OBJECTIVE:To investigate whether Jiegeng(Radix Platycodi,RP)has a Yin-Jing potentiating effect on Jingjie(Herba Schizonepetae Tenuifoliae,ST).We investigated the pharmacokinetics and tissue distribution of pulegone,th...OBJECTIVE:To investigate whether Jiegeng(Radix Platycodi,RP)has a Yin-Jing potentiating effect on Jingjie(Herba Schizonepetae Tenuifoliae,ST).We investigated the pharmacokinetics and tissue distribution of pulegone,the active ingredient in ST volatile oil,in rats to verify the scientific validity of the Yin-Jing doctrine,the basic theory of Traditional Chinese Medicine(TCM).METHODS:The volatile oil and aqueous extract of ST were extracted by hydrodistillation.RP's aqueous extract underwent aqueous extraction.After individual and co-administration,we conducted pharmacokinetic and tissue distribution studies on Sprague-Dawley male rats.RESULTS:Peak concentration(Cmax),mean retention time from 0 to∞(MRT0→∞),and area under the curve(AUC0→10),(AUC0→∞)were 1.51,1.14,2.34,and 3.86 times higher in the co-administration group than in the individual administration group,respectively(P<0.05).In addition,half-life(T1/2)was significantly prolonged in the co-administration group(P<0.05).Meanwhile,the clearance and elimination rate constant(Ke)in the co-administration group were significantly lower than those in the individual administration group,just 50%of those in the individual administration group(P<0.05).After co-administration of the drug,the pulegone content in all tissues of the rats was elevated to varying degrees,especially a significant increase in the drug content in lung tissues(P<0.05).CONCLUSION:After co-administration,the retention of pulegone in the body was prolonged,the elimination of pulegone from the body was delayed,and the accumulation of pulegone in the lungs was facilitated.Therefore,using RP as a Yin-Jing drug concoction has a significant cumulative effect of inducing upward mobilization and targeting lung tissues.展开更多
Objective:Unlike for drug-drug interactions,rigorous guidelines for assessing herb-drug interactions are nonexistent.GuHong is an intravenous herbal formulation used as adjunct therapy for the management of ischemic s...Objective:Unlike for drug-drug interactions,rigorous guidelines for assessing herb-drug interactions are nonexistent.GuHong is an intravenous herbal formulation used as adjunct therapy for the management of ischemic stroke.This investigation aimed to evaluate its potential to precipitate pharmacokinetic drug interactions.To facilitate the potential assessment,a human multi-compound pharmacokinetic study,along with associated supportive studies,was conducted to pinpoint GuHong compounds for testing.Methods:After analyzing the chemical composition of GuHong,a pharmacokinetic study was conducted in healthy subjects who received GuHong intravenously to identify its significantly exposed compounds and their pharmacokinetics.In addition,supportive rat and in vitro studies were conducted to assess the hepatic and renal disposition of these compounds,including their metabolism and transport.The potential of GuHong to precipitate drug interactions was evaluated in vitro using significantly exposed compounds,which were tested for their effects on drug-metabolizing enzymes and drug transporters listed in the ICH M12 Guideline(2024),with a focus on inhibition and induction.Samples were analyzed by liquid chromatography-mass spectrometry.Results:A total of 54 constituents(0.01-27.18μmol/day)derived from Carthamus tinctorius flowers(Honghua)and N-acetyl-L-glutamine(3,090μmol/day)were detected in GuHong.Following intravenous administration of GuHong,hydroxysafflor yellow A emerged as the principal circulating compound from Honghua.Saffloquinoside D,kaempferol-3-O-rutinoside,kaempferol-3-O-sophoroside,8-hydroxycinnamic acid-8-O-glucoside,coumaric acid-4-O-glucoside,and chlorogenic acid,also from Honghua,were detected but at low plasma levels.Hydroxysafflor yellow A,primarily eliminated via glomerular filtration-based renal excretion,exhibited the characteristics of an intravenous“hard drug.”N-Acetyl-L-glutamine was another major circulating compound of GuHong and was eliminated through renal excretion and hydrolysis to L-glutamine.GuHong had a low potential to precipitate pharmacokinetic drug interactions.Conclusions:The low drug interaction potential of GuHong is advantageous for its use in the treatment of ischemic stroke in the context of polypharmacy.The methodology developed here can be applied to the study of other complex herbal medicines for their pharmacokinetic drug interaction potential.展开更多
This study investigates the pharmacokinetics and metabolic characteristics of three marinederived piericidins as potential drug leads for kidney disease:piericidin A(PA)and its two glycosides(GPAs),glucopiericidin A(G...This study investigates the pharmacokinetics and metabolic characteristics of three marinederived piericidins as potential drug leads for kidney disease:piericidin A(PA)and its two glycosides(GPAs),glucopiericidin A(GPA)and 13-hydroxyglucopiericidin A(13-OH-GPA).The research aims to facilitate lead selection and optimization for developing a viable preclinical candidate.Rapid absorption of PA and GPAs in mice was observed,characterized by short half-lives and low bioavailability.Glycosides and hydroxyl groups significantly enhanced the absorption rate(13-OH-GPA>GPA>PA).PA and GPAs exhibited metabolic instability in liver microsomes due to Cytochrome P450 enzymes(CYPs)and uridine diphosphoglucuronosyl transferases(UGTs).Glucuronidation emerged as the primary metabolic pathway,with UGT1A7,UGT1A8,UGT1A9,and UGT1A10 demonstrating high elimination rates(30%-70%)for PA and GPAs.This rapid glucuronidation may contribute to the low bioavailability of GPAs.Despite its low bioavailability(2.69%),13-OH-GPA showed higher kidney distribution(19.8%)compared to PA(10.0%)and GPA(7.3%),suggesting enhanced biological efficacy in kidney diseases.Modifying the C-13 hydroxyl group appears to be a promising approach to improve bioavailability.In conclusion,this study provides valuable metabolic insights for the development and optimization of marine-derived piericidins as potential drug leads for kidney disease.展开更多
Background:Chiglitazar is a novel pan-agonist that can activate all three subtypes of peroxisome proliferator-activated receptor.It was approved for the treatment of type 2 diabetes mellitus as monotherapy on October ...Background:Chiglitazar is a novel pan-agonist that can activate all three subtypes of peroxisome proliferator-activated receptor.It was approved for the treatment of type 2 diabetes mellitus as monotherapy on October 19,2021,and as combination therapy with metformin when using metformin alone failed in blood glucose control on July 16,2024,by the National Medical Products Administration(NMPA)in China.However,pharmacokinetic(PK)study of this product in patients with renal impairment have not yet been conducted.The purpose of this study is to evaluate the effects of renal impairment on the PK and safety after a single oral dose of Chiglitazar.Methods:This multicenter,open-label,parallel-controlled,single-dose Phase I clinical trial(NCT 05515458)enrolled 24 participants(12/group)with severe renal impairment(SRI)or normal renal function(NRF).All participants received a single oral dose of 48 mg chiglitazar after breakfast and the PK and safety was evaluated.Results:The median Tmax was similar in both SRI and NRF groups(5.01 vs.5.02 hours).The geometric mean ratios(GMR)for Cmax,AUC0-t,and AUC0-∞were 0.807(90%confidence interval[CI]:0.697–0.935),0.853(90%CI:0.713–1.02),and 0.855(90%CI:0.716–1.02),respectively,indicating that SRI did not significantly affect the exposure of chiglitazar.The Cmax was weakly positively correlated with eGFR(r=0.4798,P=0.0177)and creatinine clearance rate(r=0.4667,P=0.0215).Urinary excretion of chiglitazar was negligible in the SRI group,with average values of Ae0-t=2,900 ng,Fe0-t=0.0060%,and CLR=0.323 mL/h within 0–72 hours post-dose.The treatment-emergent adverse event(TEAE)incidence in the SRI group(16.7%,2/12)was comparable to that in the NRF group(25%,3/12).All TEAEs were of mild severity and were adjudicated by the investigators to be unrelated to chiglitazar.No serious AE were reported.Chiglitazar exhibits a favorable safety profile.Conclusion:Severe renal impairment does not significantly affect the PK and safety of chiglitazar,and no dose adjustment for mild,moderate,and severe renal impairments is required.展开更多
Background:Building upon our previous work that developed a folate receptor-mediated,euphaorbia factor L1-loaded PLGA microsphere system integrating active and magnetic targeting for theranostics,further investigation...Background:Building upon our previous work that developed a folate receptor-mediated,euphaorbia factor L1-loaded PLGA microsphere system integrating active and magnetic targeting for theranostics,further investigation into its in vivo pharmacokinetics and tissue distribution is warranted despite its demonstrated biocompatibility and safety.Methods:A UPLC-MS/MS method was established to determine the concentration of euphorbia sterol in rat plasma and mouse tissue homogenates,healthy male SD rats and KM mice were administered in groups,drug concentrations at different time points were determined,pharmacokinetic parameters were analyzed by DAS software,and data were processed by SAS software.Results:The proposed method met the requirements of biological sample detection.The plasma pharmacokinetics of rats showed that the drug concentration in the microsphere group was lower than that in the injection group,and the parameters such as mean residence time(MRT(0–t)),half-life(T1/2z)and apparent volume of distribution(Vz)were significantly different from those in the solution group.The distribution of mouse tissues showed that the drug concentrations in the liver and lung tissues of the microsphere preparation group were higher than those in the injection group,and the drug concentrations in the lung and liver tissues were more distributed.Conclusion:The targeted drug delivery system changed the pharmacokinetic behavior and tissue distribution of euphorbia sterol,slowed down plasma elimination,prolonged the half-life,and improved the targeting of drugs in lung and liver tissues and the magnetic targeting effect of lungs.展开更多
BACKGROUND Ulcerative colitis(UC)is a chronic inflammatory condition requiring continuous treatment and monitoring.There is limited pharmacokinetic data on vedolizumab during maintenance therapy and the effect of thio...BACKGROUND Ulcerative colitis(UC)is a chronic inflammatory condition requiring continuous treatment and monitoring.There is limited pharmacokinetic data on vedolizumab during maintenance therapy and the effect of thiopurines on vedolizumab trough concentrations is unknown.AIM To investigate the exposure-response relationship of vedolizumab and the impact of thiopurine withdrawal in UC patients who have achieved sustained clinical and endoscopic remission during maintenance therapy.METHODS This is a post-hoc analysis of prospective randomized clinical trial(VIEWS)involving UC patients across 8 centers in Australia from 2018 to 2022.Patients in clinical and endoscopic remission were randomized to continue or withdraw thiopurine while receiving vedolizumab.We evaluated vedolizumab serum trough concentrations,presence of anti-vedolizumab antibodies,and clinical outcomes over 48 weeks to assess exposure-response asso-ciation and impact of thiopurine withdrawal.RESULTS There were 62 UC participants with mean age of 43.4 years and 42%were females.All participants received vedolizumab as maintenance therapy with 67.7%withdrew thiopurine.Vedolizumab serum trough concentrations remained stable over 48 weeks regardless of thiopurine use,with no anti-vedolizumab antibodies detected.Pa-tients with clinical remission had higher trough concentrations at week 48.In quartile analysis,a threshold of>11.3μg/mL was associated with sustained clinical remission,showing a sensitivity of 82.4%,specificity of 60.0%,and an area of receiver operating characteristic of 0.71(95%CI:0.49-0.93).Patients discontinuing thiopurine required higher vedolizumab concentrations for achieving remission.CONCLUSION A positive exposure-response relationship between vedolizumab trough concentrations and UC outcomes suggests that monitoring drug levels may be beneficial.While thiopurine did not influence vedolizumab levels,its with-drawal may necessitate higher vedolizumab trough concentrations to maintain remission.展开更多
Aim To establish an RP-HPLC method for the determination of scutellarin in plasma and study its pharmacokinetics in dogs. Methods Scutellarin was given to dogs by intravenous injection and determined by RP-HPLC, the m...Aim To establish an RP-HPLC method for the determination of scutellarin in plasma and study its pharmacokinetics in dogs. Methods Scutellarin was given to dogs by intravenous injection and determined by RP-HPLC, the mean plasma concentration-time curve was plotted and pharmacokinetic parameters were calculated by program 3p87. Resu;ts The concentration-time curve of scutellarin could be fitted to three-compartment model with T1/2 pi, T1/2 α and T1/2 β being 1.05 ± 0.80 min, 6.99 + 2.76 min and 51.61 + 28.78 min, respectively, Vc being 880.1 + 508.3 mL, CL being 189.6 + 53.8 mL@ min- 1, and AUC0-90 and AUC0-∞ being 574.43 + 133.95 μg@ min@ mL - 1 and 599.34 ± 132.00μg@ min@mL- 1, respectively. Conclusion The fact that the concentrations of scutellarin in plasma declined rapidly after the medication suggested that the T1/2 of scutellarin should be taken into account in drug administration and preparation development.展开更多
Aim To develop a simple and sensitive high-performance liquid chromatographicmethod for determination of plasma concentration of cinnamic acid and pharmacokinetic study in ratsafter a single oral dose of traditional C...Aim To develop a simple and sensitive high-performance liquid chromatographicmethod for determination of plasma concentration of cinnamic acid and pharmacokinetic study in ratsafter a single oral dose of traditional Chinese medicinal preparation Zi-Shen pill. Method Plasmasamples were acidified with hydrochloric acid and extracted with ethyl acetate . Cinnamic acid wasdetermined by HPLC using a G_(18) column. A mobile phase ofmethanbl-acetonitrile-water-triethyl-amine (7:22:73 = 0.2, V/V), with the pH adjusted to 4.0 withphosphoric acid, and with a UV detector set at 340 nm. Results The standard curve was linear overthe range of 1.92- 192.0 μg·mL^(-1). The LLOQ was 1.92 μg·mL^(-1) . The RSDs of within-day andbetween-day precision were < 8%. The mean recovery was 82.0% . Conclusion After validation, themethpd has been used to investigate the pharmacokinetic profiles of the traditional Chinesemedicinal preparation Zi-Shen pill.展开更多
A new HPLC MS method to determine loratadine in human plasma was established. The method involved extracting drug with organic solvent under basic conditions. The samples were seperated by ODS column and determined ...A new HPLC MS method to determine loratadine in human plasma was established. The method involved extracting drug with organic solvent under basic conditions. The samples were seperated by ODS column and determined by mass detector. The calibration curve of loratadine was linear within the range of 0.4～100 ng·mL -1 with r=0.9995 . The recovery of this method was within 95%～104%, within day and between day RSD were less than 12%. To study the pharmacokinetics and relative bioavailability of loratadine tablets, two formulations of loratadine tablets were given to 18 healthy male volunteers according to a randomized 2 way cross over design. The C max , AUC 0 t and T max values of the two formulations were 51.89±20.18 ng·mL -1 and 52.48±22.35 ng·mL -1 ; 140.75±88.42 ng·h·mL -1 and 147.24±92.33 ng·h·mL -1 ; 0.81±0.35 h and 0.81±0.27 h respectively. Results from statistic analysis showed that there were no significant difference between the C max , AUC 0-t and T max values of the two formulations. The relative bioavailability of tablets I with respect to tablets II was 97%±13% from the AUC 0 t measurement. Bioequivalance was observed between the two tablets.展开更多
To evaluate the effect of components in Guanxin Ⅱ prescription on the pharmacokinetic profiles of paeoniflorin. Plasma concentration of Paeoniflorin in rats after intravenous injection of Paronia Pall Extract （PPE）...To evaluate the effect of components in Guanxin Ⅱ prescription on the pharmacokinetic profiles of paeoniflorin. Plasma concentration of Paeoniflorin in rats after intravenous injection of Paronia Pall Extract （PPE） and oral administration of PPE and three types of decoctions in Guanxin Ⅱ prescription, respectively, were determined by HPLC analyses. NONMEM （nonlinear mixed-effect modeling） method was used to analyze full set of pharmacokinetic data directly. A two-compartment model with first-order degradation in absorption compartment was employed for the data analysis. The mean of population parameters, CL1, V1, CL2, V2, Ka0, and Kal, were measured to be 0.509 L/h, 0.104 L, 0.113 L/h, 0.123 L, 0.135/h, and 0.0135/h, respectively. Inter-individual variabilities were estimated and dose formulation （DF） was identified as a significant covariate of Ka 1, Ka0, and V1. It is concluded that the pharmacokinetic behaviors of paeoniflorin in rats can alter with different dose formulations.展开更多
Aim To investigate the population pharmacokinetics of propofol administered by TCI in Chinese elderly patients. Methods Thirty-two patients with ASA Ⅰ - Ⅱ , 65 - 82 years old, undergoing selective lower abdominal op...Aim To investigate the population pharmacokinetics of propofol administered by TCI in Chinese elderly patients. Methods Thirty-two patients with ASA Ⅰ - Ⅱ , 65 - 82 years old, undergoing selective lower abdominal operation were studied. Propofol was administered by target-controlled infusion with Marsh parameter. The target plasma concentration was 3 μg＇ mL^-1. Radial arterial blood samples were collected and analyzed by reversed phase HPLC with fluorescence detection. Population pharmacokinetic modeling was performed using NONMEM. Inter-individual variability and intra-individual variability of propofol were estimated for clearances and volumes of distribution. The effects of age, body weight, lean body mass, gender, height, hemoglobin, total protein, albumin, creatinine, alanine aminotrans ferase （ALT）, and aspartate aminotransferase （AST） were investigated. The effects of coadministered opioid drugs were also studied. Results The pharmacokinetics of propofol in the Chinese elderly patients was best described by a three-compartment open model. Lean body mass was found to be a covariate for system clearance at significant level （ P 〈 0.005）. The clearance decreased linearly with age as well （ P 〈 0. 005）. The apparent volume of distribution for deep peripheral compartment （V3） was influenced by gender. Elderly female patients showed a higher value for V3. Conclusion The pharmacokinetics of propofol administered by TCI in Chinese elderly patients can be well described by a three-compartment open model. Inclusion of age, lean body mass and gender as covariates significantly improved the model. To ensure the accuracy and precision of target-controlled infusion, the population pharmacokinetic model applied to the individual patient should be adjusted reasonably.展开更多
Aim To establish a LC-MS method for determining the concentration of nifedipine in human plasma and to evaluate the pharmacokinetic characteristics of nifedipine sustained-release tablets. Methods A XB-C18 （5 μm, 4....Aim To establish a LC-MS method for determining the concentration of nifedipine in human plasma and to evaluate the pharmacokinetic characteristics of nifedipine sustained-release tablets. Methods A XB-C18 （5 μm, 4.6 mm ×150 mm） column and a mobile phase of methanol： 0.01 mol·L^-1ammonium acetate （60：40, V/V） were used to separate nifedipine, the detections was accuracy under atmosperic pressure electronic spray ionization （AP-ESI） mode and ion mass spectrum （m/z） of 314.9 [M＋H]^＋ for nifedipine, and 320.8 [M＋H]^＋ for lorazepam （Internal Standard, IS）. Results The linear range of nifedipine was 0.3 - 80 ng·mL^-1 （ r = 0.9997）, and the limit of quantitation （LOQ） was 0.3 ng·mL^-1. The nifedipine pharmacokinetic parameters after a single dose of 20 mg nifedipine sustained-release tablets test （T） or reference （R） were as the followings, t1/2 （6.73 ± 2.00） h and （7.04 ± 2.18） h, Tmax （4.28 ± 0.70） h and （4.48 ± 0.70） h, Cmax（39.66 ± 10.58） ng·mL^-1 and （40.19 ± 10.97） ng·mL^-1, AUC0-36 （391.63 ± 108.55） ng·mL^-1·h and （387.57 ± 121.51） ng·mL^-1·h, and AUC0-∞ （408.28 ± 121.16） ng·mL^-1·h and （406.15 ± 133.13） ng·mL^-1·h. The relative bioavailability of nifedipine sustained-release tablets （test） was （103.02 ± 13.93） %. Conclusion LC-MS method for the determination of concentrations of nifedipine in human plasma was sensitive and accurate, and could be used in nifedipine bioavailability and pharmacokinetic studies.展开更多
In the present study, we determined the pharmacokinetics and bioequivalence of two amlodipine tablets in Chinese male and female volunteers using HPLC-MS/IVIS method. A randomized, two-period and crossover design was ...In the present study, we determined the pharmacokinetics and bioequivalence of two amlodipine tablets in Chinese male and female volunteers using HPLC-MS/IVIS method. A randomized, two-period and crossover design was conducted in 20 healthy volunteers （14 male subjects and six female subjects）. A single dose of either the reference or test formulation was given at the start of each period. Blood samples were collected before drug administration and at 1, 2, 3, 4, 5, 6, 8, I0, 12, 24, 48, 72, 96, 120 and 144 h after drug administration. Plasma amlodipine was detected by HPLC-MS/MS method, and the pharmacokinetic parameters were analyzed using DAS 3.2.8. The developed HPLC-MS/MS method was suitable for the analysis of amlodipine in biological matrix samples. The main pharmacokinetic parameters between the trial preparation and the reference preparation met the regulatory criteria for bioequivalence, and the two preparations were both well tolerated.展开更多
The clinical pharmacokinetics of ribavirin after a single oral dose of 600 mg ribavirin tablets in healthy Chinese volunteers was studied. A rapid and simple high performance liquid chromatography （HPLC） method was ...The clinical pharmacokinetics of ribavirin after a single oral dose of 600 mg ribavirin tablets in healthy Chinese volunteers was studied. A rapid and simple high performance liquid chromatography （HPLC） method was developed to determine the ribavirin concentration in human plasma. C18 column was used for separation with a column temperature of 25℃, the mobile phase was ultrapure water adjusted to pH 3 with acetic acid at the flow rate of 1 mL/min, and the detection wavelength was set at 207 rim. The linear range of the standard curves was 50.4-2016.0 ng/mL and the lower limit of quantification （LLOQ） was 50.4 ng/mL. The relative recoveries of ribavirin were more than 90% in plasma. The RSD of the intra-day precision was less than 10% and that of inter-day was less than 15%. The pharmacokinetic parameters of ribavirin were calculated by WinNonlin. Results indicated that the two-compartment model was a better model for describing the pharmacokinetics profile of ribavirin than one-compartment model. The AUC0-t was 10807.8 h.ng/mL, the CL/F was 64879.5 mL, and the Cmax was 525.1 ng/mL. These results provided the experimental data for the development of ribavirin dosage form.展开更多
Population pharmacokinetic meta-analysis method was used in order to obtain the pharmacokinetic characteristics of risperidone and its active metabolite. Eighteen studies were selected from published papers from 1995 ...Population pharmacokinetic meta-analysis method was used in order to obtain the pharmacokinetic characteristics of risperidone and its active metabolite. Eighteen studies were selected from published papers from 1995 to 2011. A model consisted of two compartments for parent drug and one compartment for its active metabolite combined with a flexible absorption process was developed based on the meta-dataset. The population-predicted apparent clearance for risperidone and 9-hydroxyrisperidone, the active metabolite was 7.66 L/h and 7.38 L/h, and the apparent volume of distribution in the central compartment was 70.6 L and 117 L, respectively. The final model was evaluated by visual predictive check（VPC） based on 1000 times model simulation. This model was adequately used to predict clinical therapeutic drug monitoring（TDM） data from 42 Chinese inpatients. Bias（mean prediction errors, MPE） and precision（root mean squared prediction errors, RMSE） were calculated to statistically analysis the population prediction error. It was demonstrated that the model developed from the meta-dataset was reliable and can be used to facilitate the individualized treatment for a target population.展开更多
Aim To study the pharmacokinetics of remifentanil in Chinese aduh patients undergoing elective surgery and compare the results with the data already published. Methods The pharmacokinetics of remifentanil was determin...Aim To study the pharmacokinetics of remifentanil in Chinese aduh patients undergoing elective surgery and compare the results with the data already published. Methods The pharmacokinetics of remifentanil was determined in 10 aduh patients undergoing elective surgery. Remifentanil 5 - 6 μg·kg^-1 was administered within 1 min after the induction of anesthesia. One point five millilitre of arterial blood samples were collected at 0 （baseline）, 1,2, 3, 5,7, 10, 15, 20, 25, 30, 45, 60, and 90 min after drug administration. Remifentanil concentration was assayed by HPLC/MS/MS. Resuits The concentration-time course of remifentanil was best described by a two-compartment model. Total clearance （CL = 2. 149 ± 0. 431 L·min^-1） of remifentanil was greater than the normal hepatic blood flow. The distribution half-life （t1/2α） [ 1.56 ± 0. 52 min （0.73 - 2.31 ） ] and the elimination half-life （t1/2β） [22.07 ± 10.30 min （9, 71 -36.07）] were similar with those in previous reports. Volume of distribution （ Vd = 65. 766 ± 29. 100 L） was about two times greater than that reported in previous studies of other ethnics. Conclusion In the present study, the volume of distribution is significantly greater than thai reported in previous studies of other ethnics, indicating that there are some differences in the pharmacokinetics of remifentanil among different ethnics.展开更多
Aim To establish a new and sensitive HPLC-MS method for the determination ofzolmitriptan in human plasma and study the pharmacokinetics of zolmitriptan in healthy volunteers.Methods A single oral dose of 5 mg of zolmi...Aim To establish a new and sensitive HPLC-MS method for the determination ofzolmitriptan in human plasma and study the pharmacokinetics of zolmitriptan in healthy volunteers.Methods A single oral dose of 5 mg of zolmitriptan tablet was given to 20 healthy male volunteers.After dosing, blood samples were collected for a period of 24 h, and zolmitriptan concentration inplasma was analyzed by HPLC-MS. Results The plasma concentration-time course fitted well atwo-compartment open model with a lag time, giving the following pharmacokinetic parameters: T_(max)1.60 ± 0.24 h, C_(max) 9.73 ± 1.43 ng·mL^(-1). T_(1/2α)1.72±0.46 h, T_(1/2β) 4.52 + 0.97 h,and AUC_(0-t) 55.59 ± 5.12 ng·mL^(-1)·h. Conclusion The improved analytical method forzolmitriptan is rapid, sensitive and suitable for application to pharmacokinetic studies and routinedetermination of numerous samples.展开更多
Aim To evaluate the pharmacokinetics and bioequivalence of domestic pantoprazole sodium enteric-coated tablets as compared with imported pantoprazole enteric-coated tablets. Methods This was an open randomized, two pe...Aim To evaluate the pharmacokinetics and bioequivalence of domestic pantoprazole sodium enteric-coated tablets as compared with imported pantoprazole enteric-coated tablets. Methods This was an open randomized, two periods cross over study on twenty healthy male volunteers. The pantoprazole concentrations in plasma after an oral dose of 40 mg pantoprzaole preparations were determined by a HPLC-UV method. Non-compartmental method was used for the calculation of pharmacokinetic parameters. Logarithm-transformed Cmax and A UC were analyzed by the analysis of variance （ANOVA） with 90% confidence intervals. Results The main pharmacokinetics parameters of domestic pantoprazole sodium enteric-coated tablets and imported pantoprazole sodium enteric-coated tablets were as following： Cmax （3610 ± 956）, （3466 ± 1209） ng·mL^-1, tmax （3.00 ± 0.40）, （3.00 ± 0.46） h, AUC0-t （8140 ± 5065）, （8390 ± 5474） ng·h·mL^-1, AUC0-∞ （8293 ± 5094）, （8625 ± 5606） ng·h·mL^-1, t1/2 （1.61 ± 0.28）, （1.85 ± 0.27） h, respectively. Conclusion Domestic pantoprazole sodium enteric-coated tablets were bioequivalent with the imported pantoprazole sodium enteric-coated tablets.展开更多
In the present study, we aimed to investigate the effect of CYP3A4＊ 18 genotype on the pharmacokinetics of zolpidem in healthy Chinese Hui volunteers. Blood samples were collected from volunteers for CYP3A4 genotypin...In the present study, we aimed to investigate the effect of CYP3A4＊ 18 genotype on the pharmacokinetics of zolpidem in healthy Chinese Hui volunteers. Blood samples were collected from volunteers for CYP3A4 genotyping using a polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP） assay. A pharmacokinetic study was then carried out in three groups with CYP3A4＊1/＊1 （n = 6）, CYP3A4＊1/＊18 （n = 6） and CYP3A4＊18/＊18 （n = 6） genotypes. Plasma levels of zolpidem were determined by HPLC-FLD method before and after a single oral dose of 10 mg zolpidem tartrate tablet. Significant differences were observed in the pharmacokinetic parameters of zolpidem among the three genotype groups （P〈0.05）. Compared with the CYP3A4＊1/＊1 group, the Cm,x of zolpidem in ＊1/＊18 and ＊18/＊18 groups （mean, 95% CI） was 0.89 （0.65-1.12） and 0.57 （0.47-0.66）, respectively, and the AUC0-1 in the ＊1/＊18 and ＊18/＊18 groups （mean, 95% CI） was 0.74 （0.22-1.26） and 0.61 （0.24-0.98）, respectively. There was a significant trend towards lower Cmax and AUC0-1 values of zolpidem in individuals with more CYP3A＊ 18 alleles, suggesting a gene-dosage effect. The study demonstrated that the CYP3A4＊ 18 allele played an important role in the pharmacokinetics of the zolpidem after oral administration.展开更多
Ahn To develop a high resolution HPLC method for the determination of ondansetron in human plasma and to study the pharmacokinetics of ondansetron in orally disintegrating tablets. Methods HPLC determination involved ...Ahn To develop a high resolution HPLC method for the determination of ondansetron in human plasma and to study the pharmacokinetics of ondansetron in orally disintegrating tablets. Methods HPLC determination involved liquid-liquid extraction, separation on a CN column and ultraviolet detection at 310 ran with granisetron as an internal standard. Pharmacokinetics and bioequivalence of ondansetron in orally disintegrating tablets by direct compression and conventional 8 mg tablets were evaluated and compared in 20 healthy human male volunteers after a single oral dose in a randomized cross-over study. Results The limit of quantification was 0.25 ng· mL^-1. The recovery was about 85 % or over for ondan setron and about 90% for internal standard. Linearity was good within the concentration range of 0.5 - 50 ng·mL^-1 with r^2 ranging from 0.997 1 to 0.999 9. Intra- and inter-assay coefficients of variation ranged from 1.78% to 2.38% and 3.88% -5.19%, respectively. Accuracies for spiked concentrations of 2.0, 10.0, and 30.0 ng·mL^-1 were 104.7% ±4.4%, 102.2% ± 1.1%, and99.51% ±2.34%, respectively. Pharmacokinetic parameters of AUCo-t, AUCo-∞ , Cmax, Tmax, and T1/2 were 230.2 ± 78.0 ng·h·L^-1 , 265.2± 101.5 ng·h·mL^-1, 35.67 ± 8.94 ng·mL^-l, 1.51 ±0.79 h, and 5.00± 1.41 h for orally disintegrating tablets, respectively. The analysis of variance did not show any significant difference between orally disintegrating tablets and conventional tablets, and 90% confidence intervals fell within the acceptable range for bioequivalence. Conclusion High resolution HPLC method has been set up and applied in pharmacokinetic evaluation of ondansetron in orally disintegrating tablets.展开更多
基金Supported by Key Laboratory of Xin’an Medicine Open Project Fund(Anhui University of Chinese Medicine)Ministry of Education:Study on the Material Basis and Mechanism of the Buoyance of Jingjie(Herba Schizonepetae Tenuifoliae)Loaded with Jiegeng(Radix Platycodi)of Traditional Chinese Medicine(2020xayx02)Drug Regulatory Scientific Research Key Project:Establishment of a New Dissolution Method Based on Drug Absorption and its Application in Drug Quality Monitoring(AHYJ-KJ-202206,Central of Regulatory Science for Medical Products,Anhui Province)Anhui Provincial Natural Science Foundation of Anhui Province of China:to Explore the Effect and Mechanism of Immune Escape Nanopreparation Based on"Dont eat me"Signal on Tumor Photodynamic Therapy(2308085MH308)。
文摘OBJECTIVE:To investigate whether Jiegeng(Radix Platycodi,RP)has a Yin-Jing potentiating effect on Jingjie(Herba Schizonepetae Tenuifoliae,ST).We investigated the pharmacokinetics and tissue distribution of pulegone,the active ingredient in ST volatile oil,in rats to verify the scientific validity of the Yin-Jing doctrine,the basic theory of Traditional Chinese Medicine(TCM).METHODS:The volatile oil and aqueous extract of ST were extracted by hydrodistillation.RP's aqueous extract underwent aqueous extraction.After individual and co-administration,we conducted pharmacokinetic and tissue distribution studies on Sprague-Dawley male rats.RESULTS:Peak concentration(Cmax),mean retention time from 0 to∞(MRT0→∞),and area under the curve(AUC0→10),(AUC0→∞)were 1.51,1.14,2.34,and 3.86 times higher in the co-administration group than in the individual administration group,respectively(P<0.05).In addition,half-life(T1/2)was significantly prolonged in the co-administration group(P<0.05).Meanwhile,the clearance and elimination rate constant(Ke)in the co-administration group were significantly lower than those in the individual administration group,just 50%of those in the individual administration group(P<0.05).After co-administration of the drug,the pulegone content in all tissues of the rats was elevated to varying degrees,especially a significant increase in the drug content in lung tissues(P<0.05).CONCLUSION:After co-administration,the retention of pulegone in the body was prolonged,the elimination of pulegone from the body was delayed,and the accumulation of pulegone in the lungs was facilitated.Therefore,using RP as a Yin-Jing drug concoction has a significant cumulative effect of inducing upward mobilization and targeting lung tissues.
基金supported in part by the National Natural Science Foundation of China Grants(82192912 and 82074273)by the National Key R&D Program(“Strategic Scientific and Technological Innovation Cooperation”)Key Project(2022YFE0203600)released by the Ministry of Science and Technology。
文摘Objective:Unlike for drug-drug interactions,rigorous guidelines for assessing herb-drug interactions are nonexistent.GuHong is an intravenous herbal formulation used as adjunct therapy for the management of ischemic stroke.This investigation aimed to evaluate its potential to precipitate pharmacokinetic drug interactions.To facilitate the potential assessment,a human multi-compound pharmacokinetic study,along with associated supportive studies,was conducted to pinpoint GuHong compounds for testing.Methods:After analyzing the chemical composition of GuHong,a pharmacokinetic study was conducted in healthy subjects who received GuHong intravenously to identify its significantly exposed compounds and their pharmacokinetics.In addition,supportive rat and in vitro studies were conducted to assess the hepatic and renal disposition of these compounds,including their metabolism and transport.The potential of GuHong to precipitate drug interactions was evaluated in vitro using significantly exposed compounds,which were tested for their effects on drug-metabolizing enzymes and drug transporters listed in the ICH M12 Guideline(2024),with a focus on inhibition and induction.Samples were analyzed by liquid chromatography-mass spectrometry.Results:A total of 54 constituents(0.01-27.18μmol/day)derived from Carthamus tinctorius flowers(Honghua)and N-acetyl-L-glutamine(3,090μmol/day)were detected in GuHong.Following intravenous administration of GuHong,hydroxysafflor yellow A emerged as the principal circulating compound from Honghua.Saffloquinoside D,kaempferol-3-O-rutinoside,kaempferol-3-O-sophoroside,8-hydroxycinnamic acid-8-O-glucoside,coumaric acid-4-O-glucoside,and chlorogenic acid,also from Honghua,were detected but at low plasma levels.Hydroxysafflor yellow A,primarily eliminated via glomerular filtration-based renal excretion,exhibited the characteristics of an intravenous“hard drug.”N-Acetyl-L-glutamine was another major circulating compound of GuHong and was eliminated through renal excretion and hydrolysis to L-glutamine.GuHong had a low potential to precipitate pharmacokinetic drug interactions.Conclusions:The low drug interaction potential of GuHong is advantageous for its use in the treatment of ischemic stroke in the context of polypharmacy.The methodology developed here can be applied to the study of other complex herbal medicines for their pharmacokinetic drug interaction potential.
基金supported by the Special Project for Marine Economic Development of Department of Natural Resources of Guangdong Province(No.GDNRC[2024]25)National Natural Science Foundation of China(Nos.82274002,U20A20101)+1 种基金Guangdong Local Innovation Team Program(No.2019BT02Y262)Science and Technology Innovation Project of Guangdong Medical Products Administration(Nos.S2021ZDZ042,2023ZDZ06,2024-ZDZ08,2024A1515012477)。
文摘This study investigates the pharmacokinetics and metabolic characteristics of three marinederived piericidins as potential drug leads for kidney disease:piericidin A(PA)and its two glycosides(GPAs),glucopiericidin A(GPA)and 13-hydroxyglucopiericidin A(13-OH-GPA).The research aims to facilitate lead selection and optimization for developing a viable preclinical candidate.Rapid absorption of PA and GPAs in mice was observed,characterized by short half-lives and low bioavailability.Glycosides and hydroxyl groups significantly enhanced the absorption rate(13-OH-GPA>GPA>PA).PA and GPAs exhibited metabolic instability in liver microsomes due to Cytochrome P450 enzymes(CYPs)and uridine diphosphoglucuronosyl transferases(UGTs).Glucuronidation emerged as the primary metabolic pathway,with UGT1A7,UGT1A8,UGT1A9,and UGT1A10 demonstrating high elimination rates(30%-70%)for PA and GPAs.This rapid glucuronidation may contribute to the low bioavailability of GPAs.Despite its low bioavailability(2.69%),13-OH-GPA showed higher kidney distribution(19.8%)compared to PA(10.0%)and GPA(7.3%),suggesting enhanced biological efficacy in kidney diseases.Modifying the C-13 hydroxyl group appears to be a promising approach to improve bioavailability.In conclusion,this study provides valuable metabolic insights for the development and optimization of marine-derived piericidins as potential drug leads for kidney disease.
文摘Background:Chiglitazar is a novel pan-agonist that can activate all three subtypes of peroxisome proliferator-activated receptor.It was approved for the treatment of type 2 diabetes mellitus as monotherapy on October 19,2021,and as combination therapy with metformin when using metformin alone failed in blood glucose control on July 16,2024,by the National Medical Products Administration(NMPA)in China.However,pharmacokinetic(PK)study of this product in patients with renal impairment have not yet been conducted.The purpose of this study is to evaluate the effects of renal impairment on the PK and safety after a single oral dose of Chiglitazar.Methods:This multicenter,open-label,parallel-controlled,single-dose Phase I clinical trial(NCT 05515458)enrolled 24 participants(12/group)with severe renal impairment(SRI)or normal renal function(NRF).All participants received a single oral dose of 48 mg chiglitazar after breakfast and the PK and safety was evaluated.Results:The median Tmax was similar in both SRI and NRF groups(5.01 vs.5.02 hours).The geometric mean ratios(GMR)for Cmax,AUC0-t,and AUC0-∞were 0.807(90%confidence interval[CI]:0.697–0.935),0.853(90%CI:0.713–1.02),and 0.855(90%CI:0.716–1.02),respectively,indicating that SRI did not significantly affect the exposure of chiglitazar.The Cmax was weakly positively correlated with eGFR(r=0.4798,P=0.0177)and creatinine clearance rate(r=0.4667,P=0.0215).Urinary excretion of chiglitazar was negligible in the SRI group,with average values of Ae0-t=2,900 ng,Fe0-t=0.0060%,and CLR=0.323 mL/h within 0–72 hours post-dose.The treatment-emergent adverse event(TEAE)incidence in the SRI group(16.7%,2/12)was comparable to that in the NRF group(25%,3/12).All TEAEs were of mild severity and were adjudicated by the investigators to be unrelated to chiglitazar.No serious AE were reported.Chiglitazar exhibits a favorable safety profile.Conclusion:Severe renal impairment does not significantly affect the PK and safety of chiglitazar,and no dose adjustment for mild,moderate,and severe renal impairments is required.
基金sponsored by the Fundamental Research Funds forthe Central Universities(No.2024-JYB-JBZD-047)High Level Key Discipline Construction of Traditional Chinese Medicine(zyyzdxk-2023272).
文摘Background:Building upon our previous work that developed a folate receptor-mediated,euphaorbia factor L1-loaded PLGA microsphere system integrating active and magnetic targeting for theranostics,further investigation into its in vivo pharmacokinetics and tissue distribution is warranted despite its demonstrated biocompatibility and safety.Methods:A UPLC-MS/MS method was established to determine the concentration of euphorbia sterol in rat plasma and mouse tissue homogenates,healthy male SD rats and KM mice were administered in groups,drug concentrations at different time points were determined,pharmacokinetic parameters were analyzed by DAS software,and data were processed by SAS software.Results:The proposed method met the requirements of biological sample detection.The plasma pharmacokinetics of rats showed that the drug concentration in the microsphere group was lower than that in the injection group,and the parameters such as mean residence time(MRT(0–t)),half-life(T1/2z)and apparent volume of distribution(Vz)were significantly different from those in the solution group.The distribution of mouse tissues showed that the drug concentrations in the liver and lung tissues of the microsphere preparation group were higher than those in the injection group,and the drug concentrations in the lung and liver tissues were more distributed.Conclusion:The targeted drug delivery system changed the pharmacokinetic behavior and tissue distribution of euphorbia sterol,slowed down plasma elimination,prolonged the half-life,and improved the targeting of drugs in lung and liver tissues and the magnetic targeting effect of lungs.
基金Supported by Takeda Australia,No.IISR-2016-101883.
文摘BACKGROUND Ulcerative colitis(UC)is a chronic inflammatory condition requiring continuous treatment and monitoring.There is limited pharmacokinetic data on vedolizumab during maintenance therapy and the effect of thiopurines on vedolizumab trough concentrations is unknown.AIM To investigate the exposure-response relationship of vedolizumab and the impact of thiopurine withdrawal in UC patients who have achieved sustained clinical and endoscopic remission during maintenance therapy.METHODS This is a post-hoc analysis of prospective randomized clinical trial(VIEWS)involving UC patients across 8 centers in Australia from 2018 to 2022.Patients in clinical and endoscopic remission were randomized to continue or withdraw thiopurine while receiving vedolizumab.We evaluated vedolizumab serum trough concentrations,presence of anti-vedolizumab antibodies,and clinical outcomes over 48 weeks to assess exposure-response asso-ciation and impact of thiopurine withdrawal.RESULTS There were 62 UC participants with mean age of 43.4 years and 42%were females.All participants received vedolizumab as maintenance therapy with 67.7%withdrew thiopurine.Vedolizumab serum trough concentrations remained stable over 48 weeks regardless of thiopurine use,with no anti-vedolizumab antibodies detected.Pa-tients with clinical remission had higher trough concentrations at week 48.In quartile analysis,a threshold of>11.3μg/mL was associated with sustained clinical remission,showing a sensitivity of 82.4%,specificity of 60.0%,and an area of receiver operating characteristic of 0.71(95%CI:0.49-0.93).Patients discontinuing thiopurine required higher vedolizumab concentrations for achieving remission.CONCLUSION A positive exposure-response relationship between vedolizumab trough concentrations and UC outcomes suggests that monitoring drug levels may be beneficial.While thiopurine did not influence vedolizumab levels,its with-drawal may necessitate higher vedolizumab trough concentrations to maintain remission.
文摘Aim To establish an RP-HPLC method for the determination of scutellarin in plasma and study its pharmacokinetics in dogs. Methods Scutellarin was given to dogs by intravenous injection and determined by RP-HPLC, the mean plasma concentration-time curve was plotted and pharmacokinetic parameters were calculated by program 3p87. Resu;ts The concentration-time curve of scutellarin could be fitted to three-compartment model with T1/2 pi, T1/2 α and T1/2 β being 1.05 ± 0.80 min, 6.99 + 2.76 min and 51.61 + 28.78 min, respectively, Vc being 880.1 + 508.3 mL, CL being 189.6 + 53.8 mL@ min- 1, and AUC0-90 and AUC0-∞ being 574.43 + 133.95 μg@ min@ mL - 1 and 599.34 ± 132.00μg@ min@mL- 1, respectively. Conclusion The fact that the concentrations of scutellarin in plasma declined rapidly after the medication suggested that the T1/2 of scutellarin should be taken into account in drug administration and preparation development.
文摘Aim To develop a simple and sensitive high-performance liquid chromatographicmethod for determination of plasma concentration of cinnamic acid and pharmacokinetic study in ratsafter a single oral dose of traditional Chinese medicinal preparation Zi-Shen pill. Method Plasmasamples were acidified with hydrochloric acid and extracted with ethyl acetate . Cinnamic acid wasdetermined by HPLC using a G_(18) column. A mobile phase ofmethanbl-acetonitrile-water-triethyl-amine (7:22:73 = 0.2, V/V), with the pH adjusted to 4.0 withphosphoric acid, and with a UV detector set at 340 nm. Results The standard curve was linear overthe range of 1.92- 192.0 μg·mL^(-1). The LLOQ was 1.92 μg·mL^(-1) . The RSDs of within-day andbetween-day precision were < 8%. The mean recovery was 82.0% . Conclusion After validation, themethpd has been used to investigate the pharmacokinetic profiles of the traditional Chinesemedicinal preparation Zi-Shen pill.
文摘A new HPLC MS method to determine loratadine in human plasma was established. The method involved extracting drug with organic solvent under basic conditions. The samples were seperated by ODS column and determined by mass detector. The calibration curve of loratadine was linear within the range of 0.4～100 ng·mL -1 with r=0.9995 . The recovery of this method was within 95%～104%, within day and between day RSD were less than 12%. To study the pharmacokinetics and relative bioavailability of loratadine tablets, two formulations of loratadine tablets were given to 18 healthy male volunteers according to a randomized 2 way cross over design. The C max , AUC 0 t and T max values of the two formulations were 51.89±20.18 ng·mL -1 and 52.48±22.35 ng·mL -1 ; 140.75±88.42 ng·h·mL -1 and 147.24±92.33 ng·h·mL -1 ; 0.81±0.35 h and 0.81±0.27 h respectively. Results from statistic analysis showed that there were no significant difference between the C max , AUC 0-t and T max values of the two formulations. The relative bioavailability of tablets I with respect to tablets II was 97%±13% from the AUC 0 t measurement. Bioequivalance was observed between the two tablets.
基金National Natural Science Foundation (Grant No. 30472165)
文摘To evaluate the effect of components in Guanxin Ⅱ prescription on the pharmacokinetic profiles of paeoniflorin. Plasma concentration of Paeoniflorin in rats after intravenous injection of Paronia Pall Extract （PPE） and oral administration of PPE and three types of decoctions in Guanxin Ⅱ prescription, respectively, were determined by HPLC analyses. NONMEM （nonlinear mixed-effect modeling） method was used to analyze full set of pharmacokinetic data directly. A two-compartment model with first-order degradation in absorption compartment was employed for the data analysis. The mean of population parameters, CL1, V1, CL2, V2, Ka0, and Kal, were measured to be 0.509 L/h, 0.104 L, 0.113 L/h, 0.123 L, 0.135/h, and 0.0135/h, respectively. Inter-individual variabilities were estimated and dose formulation （DF） was identified as a significant covariate of Ka 1, Ka0, and V1. It is concluded that the pharmacokinetic behaviors of paeoniflorin in rats can alter with different dose formulations.
文摘Aim To investigate the population pharmacokinetics of propofol administered by TCI in Chinese elderly patients. Methods Thirty-two patients with ASA Ⅰ - Ⅱ , 65 - 82 years old, undergoing selective lower abdominal operation were studied. Propofol was administered by target-controlled infusion with Marsh parameter. The target plasma concentration was 3 μg＇ mL^-1. Radial arterial blood samples were collected and analyzed by reversed phase HPLC with fluorescence detection. Population pharmacokinetic modeling was performed using NONMEM. Inter-individual variability and intra-individual variability of propofol were estimated for clearances and volumes of distribution. The effects of age, body weight, lean body mass, gender, height, hemoglobin, total protein, albumin, creatinine, alanine aminotrans ferase （ALT）, and aspartate aminotransferase （AST） were investigated. The effects of coadministered opioid drugs were also studied. Results The pharmacokinetics of propofol in the Chinese elderly patients was best described by a three-compartment open model. Lean body mass was found to be a covariate for system clearance at significant level （ P 〈 0.005）. The clearance decreased linearly with age as well （ P 〈 0. 005）. The apparent volume of distribution for deep peripheral compartment （V3） was influenced by gender. Elderly female patients showed a higher value for V3. Conclusion The pharmacokinetics of propofol administered by TCI in Chinese elderly patients can be well described by a three-compartment open model. Inclusion of age, lean body mass and gender as covariates significantly improved the model. To ensure the accuracy and precision of target-controlled infusion, the population pharmacokinetic model applied to the individual patient should be adjusted reasonably.
文摘Aim To establish a LC-MS method for determining the concentration of nifedipine in human plasma and to evaluate the pharmacokinetic characteristics of nifedipine sustained-release tablets. Methods A XB-C18 （5 μm, 4.6 mm ×150 mm） column and a mobile phase of methanol： 0.01 mol·L^-1ammonium acetate （60：40, V/V） were used to separate nifedipine, the detections was accuracy under atmosperic pressure electronic spray ionization （AP-ESI） mode and ion mass spectrum （m/z） of 314.9 [M＋H]^＋ for nifedipine, and 320.8 [M＋H]^＋ for lorazepam （Internal Standard, IS）. Results The linear range of nifedipine was 0.3 - 80 ng·mL^-1 （ r = 0.9997）, and the limit of quantitation （LOQ） was 0.3 ng·mL^-1. The nifedipine pharmacokinetic parameters after a single dose of 20 mg nifedipine sustained-release tablets test （T） or reference （R） were as the followings, t1/2 （6.73 ± 2.00） h and （7.04 ± 2.18） h, Tmax （4.28 ± 0.70） h and （4.48 ± 0.70） h, Cmax（39.66 ± 10.58） ng·mL^-1 and （40.19 ± 10.97） ng·mL^-1, AUC0-36 （391.63 ± 108.55） ng·mL^-1·h and （387.57 ± 121.51） ng·mL^-1·h, and AUC0-∞ （408.28 ± 121.16） ng·mL^-1·h and （406.15 ± 133.13） ng·mL^-1·h. The relative bioavailability of nifedipine sustained-release tablets （test） was （103.02 ± 13.93） %. Conclusion LC-MS method for the determination of concentrations of nifedipine in human plasma was sensitive and accurate, and could be used in nifedipine bioavailability and pharmacokinetic studies.
基金supported by Institute of Clinical Pharmacy,Central South University,Changsha,China
文摘In the present study, we determined the pharmacokinetics and bioequivalence of two amlodipine tablets in Chinese male and female volunteers using HPLC-MS/IVIS method. A randomized, two-period and crossover design was conducted in 20 healthy volunteers （14 male subjects and six female subjects）. A single dose of either the reference or test formulation was given at the start of each period. Blood samples were collected before drug administration and at 1, 2, 3, 4, 5, 6, 8, I0, 12, 24, 48, 72, 96, 120 and 144 h after drug administration. Plasma amlodipine was detected by HPLC-MS/MS method, and the pharmacokinetic parameters were analyzed using DAS 3.2.8. The developed HPLC-MS/MS method was suitable for the analysis of amlodipine in biological matrix samples. The main pharmacokinetic parameters between the trial preparation and the reference preparation met the regulatory criteria for bioequivalence, and the two preparations were both well tolerated.
文摘The clinical pharmacokinetics of ribavirin after a single oral dose of 600 mg ribavirin tablets in healthy Chinese volunteers was studied. A rapid and simple high performance liquid chromatography （HPLC） method was developed to determine the ribavirin concentration in human plasma. C18 column was used for separation with a column temperature of 25℃, the mobile phase was ultrapure water adjusted to pH 3 with acetic acid at the flow rate of 1 mL/min, and the detection wavelength was set at 207 rim. The linear range of the standard curves was 50.4-2016.0 ng/mL and the lower limit of quantification （LLOQ） was 50.4 ng/mL. The relative recoveries of ribavirin were more than 90% in plasma. The RSD of the intra-day precision was less than 10% and that of inter-day was less than 15%. The pharmacokinetic parameters of ribavirin were calculated by WinNonlin. Results indicated that the two-compartment model was a better model for describing the pharmacokinetics profile of ribavirin than one-compartment model. The AUC0-t was 10807.8 h.ng/mL, the CL/F was 64879.5 mL, and the Cmax was 525.1 ng/mL. These results provided the experimental data for the development of ribavirin dosage form.
基金Guangzhou Municipality Medical and Technology Project(Grant No.20131A011087)Beijing Key Lab of Diagnostics and Therapeutics for Psychiatric disorders 2013 Open Foundation(Grant No.2013JSJB01)Beijing Municipal Education Commission Science and Technology Development Program(Grant No.KM201110025025)
文摘Population pharmacokinetic meta-analysis method was used in order to obtain the pharmacokinetic characteristics of risperidone and its active metabolite. Eighteen studies were selected from published papers from 1995 to 2011. A model consisted of two compartments for parent drug and one compartment for its active metabolite combined with a flexible absorption process was developed based on the meta-dataset. The population-predicted apparent clearance for risperidone and 9-hydroxyrisperidone, the active metabolite was 7.66 L/h and 7.38 L/h, and the apparent volume of distribution in the central compartment was 70.6 L and 117 L, respectively. The final model was evaluated by visual predictive check（VPC） based on 1000 times model simulation. This model was adequately used to predict clinical therapeutic drug monitoring（TDM） data from 42 Chinese inpatients. Bias（mean prediction errors, MPE） and precision（root mean squared prediction errors, RMSE） were calculated to statistically analysis the population prediction error. It was demonstrated that the model developed from the meta-dataset was reliable and can be used to facilitate the individualized treatment for a target population.
文摘Aim To study the pharmacokinetics of remifentanil in Chinese aduh patients undergoing elective surgery and compare the results with the data already published. Methods The pharmacokinetics of remifentanil was determined in 10 aduh patients undergoing elective surgery. Remifentanil 5 - 6 μg·kg^-1 was administered within 1 min after the induction of anesthesia. One point five millilitre of arterial blood samples were collected at 0 （baseline）, 1,2, 3, 5,7, 10, 15, 20, 25, 30, 45, 60, and 90 min after drug administration. Remifentanil concentration was assayed by HPLC/MS/MS. Resuits The concentration-time course of remifentanil was best described by a two-compartment model. Total clearance （CL = 2. 149 ± 0. 431 L·min^-1） of remifentanil was greater than the normal hepatic blood flow. The distribution half-life （t1/2α） [ 1.56 ± 0. 52 min （0.73 - 2.31 ） ] and the elimination half-life （t1/2β） [22.07 ± 10.30 min （9, 71 -36.07）] were similar with those in previous reports. Volume of distribution （ Vd = 65. 766 ± 29. 100 L） was about two times greater than that reported in previous studies of other ethnics. Conclusion In the present study, the volume of distribution is significantly greater than thai reported in previous studies of other ethnics, indicating that there are some differences in the pharmacokinetics of remifentanil among different ethnics.
文摘Aim To establish a new and sensitive HPLC-MS method for the determination ofzolmitriptan in human plasma and study the pharmacokinetics of zolmitriptan in healthy volunteers.Methods A single oral dose of 5 mg of zolmitriptan tablet was given to 20 healthy male volunteers.After dosing, blood samples were collected for a period of 24 h, and zolmitriptan concentration inplasma was analyzed by HPLC-MS. Results The plasma concentration-time course fitted well atwo-compartment open model with a lag time, giving the following pharmacokinetic parameters: T_(max)1.60 ± 0.24 h, C_(max) 9.73 ± 1.43 ng·mL^(-1). T_(1/2α)1.72±0.46 h, T_(1/2β) 4.52 + 0.97 h,and AUC_(0-t) 55.59 ± 5.12 ng·mL^(-1)·h. Conclusion The improved analytical method forzolmitriptan is rapid, sensitive and suitable for application to pharmacokinetic studies and routinedetermination of numerous samples.
文摘Aim To evaluate the pharmacokinetics and bioequivalence of domestic pantoprazole sodium enteric-coated tablets as compared with imported pantoprazole enteric-coated tablets. Methods This was an open randomized, two periods cross over study on twenty healthy male volunteers. The pantoprazole concentrations in plasma after an oral dose of 40 mg pantoprzaole preparations were determined by a HPLC-UV method. Non-compartmental method was used for the calculation of pharmacokinetic parameters. Logarithm-transformed Cmax and A UC were analyzed by the analysis of variance （ANOVA） with 90% confidence intervals. Results The main pharmacokinetics parameters of domestic pantoprazole sodium enteric-coated tablets and imported pantoprazole sodium enteric-coated tablets were as following： Cmax （3610 ± 956）, （3466 ± 1209） ng·mL^-1, tmax （3.00 ± 0.40）, （3.00 ± 0.46） h, AUC0-t （8140 ± 5065）, （8390 ± 5474） ng·h·mL^-1, AUC0-∞ （8293 ± 5094）, （8625 ± 5606） ng·h·mL^-1, t1/2 （1.61 ± 0.28）, （1.85 ± 0.27） h, respectively. Conclusion Domestic pantoprazole sodium enteric-coated tablets were bioequivalent with the imported pantoprazole sodium enteric-coated tablets.
基金Funds of the Chinese Army Medical Science and Technology Research"Eleventh Five-Year Plan"Project(Grant No.06G023)
文摘In the present study, we aimed to investigate the effect of CYP3A4＊ 18 genotype on the pharmacokinetics of zolpidem in healthy Chinese Hui volunteers. Blood samples were collected from volunteers for CYP3A4 genotyping using a polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP） assay. A pharmacokinetic study was then carried out in three groups with CYP3A4＊1/＊1 （n = 6）, CYP3A4＊1/＊18 （n = 6） and CYP3A4＊18/＊18 （n = 6） genotypes. Plasma levels of zolpidem were determined by HPLC-FLD method before and after a single oral dose of 10 mg zolpidem tartrate tablet. Significant differences were observed in the pharmacokinetic parameters of zolpidem among the three genotype groups （P〈0.05）. Compared with the CYP3A4＊1/＊1 group, the Cm,x of zolpidem in ＊1/＊18 and ＊18/＊18 groups （mean, 95% CI） was 0.89 （0.65-1.12） and 0.57 （0.47-0.66）, respectively, and the AUC0-1 in the ＊1/＊18 and ＊18/＊18 groups （mean, 95% CI） was 0.74 （0.22-1.26） and 0.61 （0.24-0.98）, respectively. There was a significant trend towards lower Cmax and AUC0-1 values of zolpidem in individuals with more CYP3A＊ 18 alleles, suggesting a gene-dosage effect. The study demonstrated that the CYP3A4＊ 18 allele played an important role in the pharmacokinetics of the zolpidem after oral administration.
文摘Ahn To develop a high resolution HPLC method for the determination of ondansetron in human plasma and to study the pharmacokinetics of ondansetron in orally disintegrating tablets. Methods HPLC determination involved liquid-liquid extraction, separation on a CN column and ultraviolet detection at 310 ran with granisetron as an internal standard. Pharmacokinetics and bioequivalence of ondansetron in orally disintegrating tablets by direct compression and conventional 8 mg tablets were evaluated and compared in 20 healthy human male volunteers after a single oral dose in a randomized cross-over study. Results The limit of quantification was 0.25 ng· mL^-1. The recovery was about 85 % or over for ondan setron and about 90% for internal standard. Linearity was good within the concentration range of 0.5 - 50 ng·mL^-1 with r^2 ranging from 0.997 1 to 0.999 9. Intra- and inter-assay coefficients of variation ranged from 1.78% to 2.38% and 3.88% -5.19%, respectively. Accuracies for spiked concentrations of 2.0, 10.0, and 30.0 ng·mL^-1 were 104.7% ±4.4%, 102.2% ± 1.1%, and99.51% ±2.34%, respectively. Pharmacokinetic parameters of AUCo-t, AUCo-∞ , Cmax, Tmax, and T1/2 were 230.2 ± 78.0 ng·h·L^-1 , 265.2± 101.5 ng·h·mL^-1, 35.67 ± 8.94 ng·mL^-l, 1.51 ±0.79 h, and 5.00± 1.41 h for orally disintegrating tablets, respectively. The analysis of variance did not show any significant difference between orally disintegrating tablets and conventional tablets, and 90% confidence intervals fell within the acceptable range for bioequivalence. Conclusion High resolution HPLC method has been set up and applied in pharmacokinetic evaluation of ondansetron in orally disintegrating tablets.
