BACKGROUND Pyoderma gangrenosum(PG)is one of the most severe extra-intestinal manifest-ations of ulcerative colitis(UC).The treatment of refractory UC combined with PG is challenging,particularly for patients with sch...BACKGROUND Pyoderma gangrenosum(PG)is one of the most severe extra-intestinal manifest-ations of ulcerative colitis(UC).The treatment of refractory UC combined with PG is challenging,particularly for patients with schizophrenia(SCZ)with a long-term history of risperidone use,and there have been no successfully treated patients reported in the literature.CASE SUMMARY A 36-year-old woman attended the gastroenterological clinic due to intermittent symptoms of diarrhea and mucous bloody stools.Prior to the emergence of these symptoms,the patient had a history of SCZ for 3 years.She had been receiving long-term risperidone treatment and had stable mental symptoms.In April 2023,she was diagnosed with UC E3 moderate and began taking mesalazine 3 g/day.In March 2024,her intestinal symptoms recurred and approximately 2 months later,PG developed in both lower limbs.Previous treatments with adalimumab and steroids were ineffective for PG and UC,and simultaneously,the patient experienced headache,confusion,and severe sleep disturbances.After switching to upadacitinib(UPA)45 mg/day,PG lesions showed complete healing and fecal calprotectin was<10μg/g after 7 weeks of treatment.Following approximately 12 weeks of UPA therapy,colonoscopy indicated that the patient had achieved mucosal healing.No adverse events occurred during UPA induction and main-tenance therapy for 6 months with risperidone.CONCLUSION UPA treatment led to successful resolution of both intestinal and extra-intestinal manifestations in this patient with new-onset UC who had a history of SCZ.No adverse effects were observed with concurrent UPA and risperidone use.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
In the present study, we investigated the complexation of risperidone with hydroxypropyl-β-cyclodextrin （HP-β-CD） in aqueous solution due to the poor water solubility and low oral bioavailability of risperidone in...In the present study, we investigated the complexation of risperidone with hydroxypropyl-β-cyclodextrin （HP-β-CD） in aqueous solution due to the poor water solubility and low oral bioavailability of risperidone in humans. The effect of temperature on the complexation was examined, and thermodynamic parameters of the complexation process, such as Gibbs free energy change （AG）, enthalpy change （AH） and entropy change （AS）, were also explored. Meantime, the solid dispersion of risperidone with HP-β-CD was prepared and confirmed by Fourier IR spectroscopy and X-ray diffractometry. The experimental results suggested that the complex of the drug with HP-β-CD at a molar ratio of 1：1 could form in aqueous solution, and the complexation was an endothermic and entropy-driven process. The risperidone-HP-β-CD solid dispersion exhibited a remarkable improvement in the dissolution rate of the drug. This might be attributed to the amorphous state, the enhanced wettability as well as the complex formation of the drug with HP-β-CD in aqueous solution.展开更多
Objective To identify whether sarsasapogenin, a sapogenin from the Chinese medicinal herb Anemarrhena Asphodeloides Bunge, would augment the efficacy of risperidone and significantly improve cognitive functions in pat...Objective To identify whether sarsasapogenin, a sapogenin from the Chinese medicinal herb Anemarrhena Asphodeloides Bunge, would augment the efficacy of risperidone and significantly improve cognitive functions in patients with negative symptoms dominated schizophrenia. Methods The trial was a double-blind, placebo-controlled, parallel- group design. The eligible patients were randomized into 2 treatment groups： sarsasapogenin group （sarsasapogenin plus risperidone for 8 weeks, n = 41） and placebo group （risperidone only for 8 weeks, n = 39）. At the baseline, as well as at weeks 2, 4 and 8 of treatment, the therapeutic response was measured by using scales including Positive and Nega- tive Symptoms Scale （PANSS）, Wechsler Memory Scale （WMS）, modified Chinese Wechsler Adult Intelligence Scale （mWAIS）, Clinical Global Impression （CGI） and Brief Psychiatry Rating Scale （BPRS）. The study period for each subject was 8 weeks and duration of overall trial was 2 years. Results Patients treated with sarsasapogenin plus risperidone demonstrated no statistically significant differences in changes in PANSS, WMS or mWAIS score at the end-point of the trial compared with patients treated with placebo plus risperidone. The incidence of treatment-emergent adverse events in patients treated with sarsasapogenin was not different from that observed in placebo group. Conclusion Sarsasapogenin did not augment the efficacy of risperidone in treating negative symptoms dominated schizophrenia. Sarsasapogenin at a dosage of 200 mg per day added to a flexible dosage of risperidone at 2-4 mg per day is safe and well tolerated by patients with negative symptoms dominated schizophrenia.展开更多
Aim To investigate the NMR spectroscopy of amlodipine and risperidone.Methods 1D NMR and 2D NMR experimental techniques of gCOSY, gHSQC and gHMBC were wsed. Results Theassignments of the ~1H and ^(13) C NMR data for t...Aim To investigate the NMR spectroscopy of amlodipine and risperidone.Methods 1D NMR and 2D NMR experimental techniques of gCOSY, gHSQC and gHMBC were wsed. Results Theassignments of the ~1H and ^(13) C NMR data for the two drugs were performed and confirmed by theevidence of J_(HF) and J_(CF). Conclusion The structures of amlodipine and risperidone wereconfirmed by careful analysis of regular 1D and 2D NMR spectroscopy.展开更多
BACKGROUND Prior studies have noted great variability in the plasma levels of risperidone(RIS).Plasma concentrations of RIS and its active moiety are highly variable and depend on absorption,metabolism,and other predi...BACKGROUND Prior studies have noted great variability in the plasma levels of risperidone(RIS).Plasma concentrations of RIS and its active moiety are highly variable and depend on absorption,metabolism,and other predictors of metabolic dysregulation;however,these factors are poorly understood and the association between metabolic change and change in psychopathology is uncertain.AIM To ascertain the characteristics of chronic schizophrenic patients treated with RIS,and to assess their relationship with plasma RIS levels.METHODS This was a descriptive cross-sectional study of 50 patients with a diagnosis of schizophrenic psychosis treated with RIS in a psychiatric service.The plasma concentrations of RIS and its metabolite 9-hydroxyrisperidone were determined by high performance liquid chromatography.The patients’demographic and clinical characteristics,and psychopathologies were assessed,and the associations between clinical variables and plasma levels of RIS were explored.RESULTS Male patients received higher doses of RIS than female ones,but plasma concentrations of RIS and risperidone+9-hydroxyrisperidone(active moiety)were higher in female patients.Age and the mean scores of the general psychopathology subscale of the Positive and Negative Syndrome Scale(PANSS)were significantly positively correlated with plasma concentrations of risperidone+9-hydroxyrisperidone adjusted for weight and dose in all 50 subjects.In male subjects,we found a statistically significant positive correlation between the concentrations of risperidone+9-hydroxyrisperidone in plasma/(dose×kg)and age,mean PANSS negative subscale scores,mean PANSS general psychopathology subscale scores,and mean PANSS total scores.CONCLUSION Long-term use of RIS should be closely monitored in older patients and females to minimize the risk of high concentrations which could induce side effects.展开更多
In the present study,we aimed to determine the pharmacokinetics(PK),pharmacodynamics(PD),adverse events(AEs),and their relationships in Chinese patients with schizophrenia after a single dose of long-acting risperidon...In the present study,we aimed to determine the pharmacokinetics(PK),pharmacodynamics(PD),adverse events(AEs),and their relationships in Chinese patients with schizophrenia after a single dose of long-acting risperidone.Schizophrenic patients(six females and seven males)were enrolled in this study.Serial blood samples were collected after drug administration during 63 d,and the drug concentrations were analyzed by LC-MS/MS.Safety and tolerance were evaluated by monitoring the AEs,changes in clinical laboratory results,12-lead ECG,vital signs,physical examination,and injection-site reactions.The extrapyramidal symptoms were evaluated using the ESRS.Efficacy was evaluated by the PANSS and BPRS.Twelve out of the 13 participants completed the trial.There were few clinically meaningful changes in mean clinical laboratory values,vital signs,or ECG parameters,except for the prolactin level and body weight.There were no serious AEs,and those observed were reversible.Significant clinical improvements in PANSS and PANSS-derived BPRS total scores were observed.The mean(standard deviation,coefficient of variation)values for these PK parameters were as follows:C_(max),8.954(8.059,90.0%)ng/mL;area under the curve AUC_(0-t),2453(1156,47.1%)ng·h/mL;AUC_(0-∞),2472(1160,46.9%)ng·h/mL;t_(max),830.0(min:744.0,max:984.0,11.8%)h;and t_(1/2),68.56(10.77,15.7%)h.The PK characteristics of long-acting risperidone showed a high level of inter-individual variation,while there were no clear correlations between PK,efficacy and AEs among the patients in the present study.展开更多
This study presents a rapid, specific and sensitive liquid chromatography/tandem mass spectrometry (LC-MS/MS) assay for determination of risperidone (RIS) in human serum using paroxetine as an internal standard (IS). ...This study presents a rapid, specific and sensitive liquid chromatography/tandem mass spectrometry (LC-MS/MS) assay for determination of risperidone (RIS) in human serum using paroxetine as an internal standard (IS). An Alltima-C18 column (2.1 mm×100 mm, 3 μm) and a mobile phase consisting of 0.1% formic acid-acetonitrile (40:60, v/v) were used for separation. The analysis was performed by selected reaction monitoring (SRM) method, and the peak area of the m/z 411.3→191.1 transition for RIS was measured versus that of the m/z 330.1→192.1 transition for IS to generate the standard curves. The assay linearity of RIS was confirmed over the range 0.25～50.00 ng/ml and the limit of quantitation was 0.05 ng/ml. The linear range corresponds well with the serum concentrations of the analytes obtained in clinical pharmacokinetic studies. Intraday and interday relative standard deviations were 1.85%～9.09% and 1.56%～4.38%, respectively. The recovery of RIS from serum was in the range of 70.20%～84.50%. The method was successfully applied to investigate the bioequivalence between two kinds of tablets (test versus reference products) in 18 healthy male Chinese volunteers. The result suggests that two formulations are bioequivalent.展开更多
Dear editor, P-glycoprotein （P-gp, also known as ATP-binding cassette transport sub-family B member 1, ABCB1） is a potent ATP-dependent efflux pump for a wide variety of drugs. Although studies of its substrates are...Dear editor, P-glycoprotein （P-gp, also known as ATP-binding cassette transport sub-family B member 1, ABCB1） is a potent ATP-dependent efflux pump for a wide variety of drugs. Although studies of its substrates are abundant [ 1, 2], and ABCB1 is a well-conserved gene, there is increasing evi- dence that its polymorphisms affect substrate specificity [3]. A previous study reported that the synonymous single nucleotide polymorphism （SNP） C3435T （rs1045642） affects the timing of co-translational folding and insertionof P-gp into the membrane,展开更多
Objectives: Testing a hypothesis, that platelet cytochrome c-oxidase (COX) activities in patients with paranoid schizophrenia, acute episode, may be linked to dynamics of their clinical patterns and quality of cogniti...Objectives: Testing a hypothesis, that platelet cytochrome c-oxidase (COX) activities in patients with paranoid schizophrenia, acute episode, may be linked to dynamics of their clinical patterns and quality of cognitive functioning under antipsychotic treatment. Methods: Psychopatho-logical (PANSS, NSA-16) and cognitive assess-ments;platelet COX enzymatic activity determination, post-hoc nonparametric statistical analysis. Results: Psychopathological and cognitive assessments were done and blood was sampled in patients before (at baseline) and after treatment with risperidone. Following regu- larities were found after the treatment of patients: Significant elevation of COX, wherein the higher was COX at baseline, the more prominent was decrease in PANSSneg and NSA rates;significant negative correlation between COX and executive time in cognitive tests. When the patient group was divided by median of COX at baseline into two subgroups (greater or equal median, and 20% was assigned to the first subgroup;significantly larger amount of patients with PANSSneg by <20% was assigned to the second group. Conclusions: Therapy with risperidone seems to be more effective for patients with higher COX activity at baseline, but this fact requires further study.展开更多
Objective: To explore the different effects of paliperidone and risperidone therapy on blood lipid and Hcy metabolism as well as endocrine hormones in patients with schizophrenia. Methods: A total of 118 patients with...Objective: To explore the different effects of paliperidone and risperidone therapy on blood lipid and Hcy metabolism as well as endocrine hormones in patients with schizophrenia. Methods: A total of 118 patients with schizophrenia who were treated in the hospital between December 2014 and February 2017 were collected as the research subjects and divided into control group and study group by random number table, each group with 59 cases. Control group received risperidone therapy, observation group received paliperidone therapy, and the differences in the levels of blood lipid indexes, Hcy metabolism indexes and endocrine hormones were compared between the two groups before and after treatment. Results:There was no statistically significant difference in the levels of blood lipid indexes, Hcy and endocrine hormones between the two groups before treatment. After treatment, lipid indexes TG and TC levels in peripheral blood of study group were lower than those of control group while HDL-C content was higher than that of control group;Hcy level in serum of study group was lower than that of control group;endocrine hormones FT3, FT4, T and E2 levels in serum of study group were higher than those of control group. Conclusion: paliperidone therapy for schizophrenia can be more effective than risperidone in regulating blood lipid metabolism, Hcy metabolism and endocrine hormones.展开更多
Background Risperidone (RSP) has a rapid onset in vivo, low dosage and high plasma protein binding rate, therefore therapeutic drug monitoring (TDM) is needed to ensure safety in clinical treatment. However, compared ...Background Risperidone (RSP) has a rapid onset in vivo, low dosage and high plasma protein binding rate, therefore therapeutic drug monitoring (TDM) is needed to ensure safety in clinical treatment. However, compared with blood, hair is non-invasive, safe, non-infectious and easy to transport and store. Aims This study aims to investigate the correlations among the drug concentrations of RSP in hair and serum, which provides an experimental basis to explore hair as a novel biomaterial to meet the needs of clinical detection. Methods 34 patients with schizophrenia treated with RSP for more than 3 months were enrolled in this study. About 1 cm section of hair near the scalp was taken from the subjects, pretreated and detected by liquid chromatography-mass spectrometry. A correlation analysis was conducted among the drug concentrations in hair, the serum concentrations and the daily dosage. The data were analysed usi叩 SPSS 20.0 software. Results There was significant correlation between the hair concentration of RSP (two-tailed test, r=0.440, p=0.009) with the serum concentration of RSP, and the hair concentration of 9-hydroxyrisperidone (9-HR) with the serum concentration of 9-HR had no significant correlation (two-tailed test, r=-0.217, p=0.217);the total concentration of the RSP and 9-HR had no significant correlation between hair and serum (r=0.227, p=0.196). The dosage had no statistically significant correlation with the concentration of RSP in hair (r=0.207, p=0.241), 9-HR in hair (r=-0.194, p=0.271) and the total concentration of RSP and 9-HR in hair (r=0.188, p=0.288). There was no statistical correlation between the dosage and the concentration of RSP in serum (r=-0.059, p=0.741), but significant correlation between the dosage and 9-HR in serum (r=0.581 p<0.001) was found, and the correlation between the dosage and the total concentration of the two drugs RSP and 9-HR in serum was also significant (r=0.437, p=0.01). Conclusion The correlation analysis showed that the concentration of RSP in hair was statistically significant with the serum RSP concentration. In this study, we provided some experimental basis for hair as a new biomaterial to monitor the therapeutic drug concentration.展开更多
Inter-individual variability in oral drug efficacy and toxicity is commonly observed in all therapeutic areas.Importantly,interindividual variability in drug uptake and metabolism can result in poor drug response,adve...Inter-individual variability in oral drug efficacy and toxicity is commonly observed in all therapeutic areas.Importantly,interindividual variability in drug uptake and metabolism can result in poor drug response,adverse drug reactions,or unfavorable drug–drug interaction.One of the common causes of individual variations in drug response is genetic variation of drug transporters and metabolizing enzymes[1,2].We focus on the interplay between efflux transporter(ATP-binding cassette,subfamily B(MDR/TAP),member 1/ABCB1)and cytochrome P450s according to genetic polymorphism[3].The objective of this lecture is to investigate the combined influence of genetic polymorphisms in ABCB1 and CYP2D6 genes on risperidone pharmacokinetics[4].展开更多
Risperidone long-acting injectable (RLAI) is approved for the treatment of schizophrenia in many countries. The suggested site is the gluteal muscle with a needle length of two inches (50 mm) in Japan, which is longer...Risperidone long-acting injectable (RLAI) is approved for the treatment of schizophrenia in many countries. The suggested site is the gluteal muscle with a needle length of two inches (50 mm) in Japan, which is longer than the ordinarily used needle for intramuscular injections. The aim of this study was to determine the optimal needle insertion length for accurate delivery of RLAI procedure among subjects who have normal body mass index (BMI: 18 to 25) and high BMI (>25). Thirty-seven patients with schizophrenia were administered RLAI intramuscularly into the dorsogluteal muscle. The standard procedure required inserting 80% of the two inch needle. By using data collected by ultrasonography, the findings confirmed that the median needle insertion lengths for subjects with normal and high BMI were 39.0 and 45.5 mm, respectively. To deliver RLAI effectively and safely, the authors strongly recommend that a specialized needle be used that is “marked” at the 40 mm point from the tip of the needle to the base. In this way regardless of subcutaneous fat content, the RLAI can be safely delivered into the muscle without causing untoward or side effects.展开更多
Objective:The efficacy and occurrence of adverse reactions of prescriptions containing phlegm-resolving Chinese medicine combined with risperidone in the treatment of schizophrenia were retrospectively studied by mean...Objective:The efficacy and occurrence of adverse reactions of prescriptions containing phlegm-resolving Chinese medicine combined with risperidone in the treatment of schizophrenia were retrospectively studied by means of meta-analysis.Methods:A variety of different Chinese and English databases were searched from January 1,2000 to May 1,2020.Review Manager 5.3 software was used to evaluate the methodological quality of the included studies.The positive and negative symptom scale(PANSS)was used as the evaluation standard to analyze the total scores,positive scores,negative scores and general psychopathological scores,clinical efficacy and safety of prescriptions containing phlegmresolving Chinese medicine combined with risperidone of schizophrenia.The heterogeneity test and sensitivity analysis were also carried out by Review Manager 5.3,and the potential publication bias was analyzed by"funnel plot".Results:A total of 1515 patients were included in 15 studies.Compared with control group of risperidone alone,the total PANSS scale score,positive symptom score,negative symptom score and general psychopathological score of the treatment group of phlegm-resolving Chinese medicine combined with risperidone were all lower than those of the control group(P=0.01,MD=-6.35,95%CI[-11.29,-1.40]),(P=0.04,MD=-1.42,95%CI[-2.74,-0.09]),(P<0.01,MD=-2.16,95%CI[-3.41,-0.91]),and(P<0.01,MD=-3.80,95%CI[-6.37,-1.24]),the clinical efficacy of phlegm-resolving Chinese medicine combined with risperidone treatment group on schizophrenia was better than that of the control group[P<0.01,RR=1.09,95%CI(1.05-1.13)].The incidence of adverse reactions was reduced(P=0.02,RR=0.56,95%CI[0.34-0.93]).Conclusion:The combination of prescriptions containing phlegm-resolving Chinese medicine and risperidone can effectively improve the efficacy of patients with schizophrenia and reduce the occurrence of adverse drug reactions compared with risperidone alone.展开更多
Brain developmental disorders in humans, including Autism Spectrum Disorders (ASD) and Down’s syndrome, have been linked to increased serotonin levels. This work was designed to study changes in serotonin levels in t...Brain developmental disorders in humans, including Autism Spectrum Disorders (ASD) and Down’s syndrome, have been linked to increased serotonin levels. This work was designed to study changes in serotonin levels in the early stages of development with two classes of antipsychotic drugs: Risperidone, a drug that blocks serotonin and dopamine receptors, and fluoxetine, a serotonin reuptake inhibitor. The use of antipsychotic drugs is a solid choice to study the decrease and increase of these neurotransmitters and their influence on development. The study of these parameters will give an idea of the effects of serotonin in early developmental stages. To this end, we examined the effects of risperidone and fluoxetine on the locomotor activity, heart rate and brain development of zebrafish larvae. Our results showed that in larvae exposed to fluoxetine alone, swimming was significantly increased at 9 dpf (days post-fertilization). Erratic and abnormal movements were observed suggesting a toxic effect of fluoxetine. No erratic swimming was observed in larvae treated with fluoxetine plus risperidone. Both drugs presented morphological changes in dopaminergic neurons and mononeurons. Exposure to fluoxetine plus risperidone indicated possible reversal effects. Studies in zebrafish allow obtaining new insights into the side effects of these drugs as well as into the brain control of locomotor activity. Testing several drug-induced changes in behavior and serotonin levels is one of the experimental approaches for screening a new therapeutically relevant compound, and thus, merits further research.展开更多
We present the case of a 24-year-old man, who was a keen runner, developing chronic bilateral lower leg compartment syndrome following co-administration of Risperidone and Sodium Valproate. Having had failed medical a...We present the case of a 24-year-old man, who was a keen runner, developing chronic bilateral lower leg compartment syndrome following co-administration of Risperidone and Sodium Valproate. Having had failed medical and physical therapies, he underwent surgical decompression of his more problematic left lower leg compartments. In the interval between sequential fasciotomies, control of his psychiatric symptoms allowed the dose of his Risperidone to be reduced, resulting in a greater exercise tolerance. Ultimately he no longer required the contra-lateral lower leg compartments to be decompressed surgically. He had returned to his original level of activity with no further psychotic episodes.展开更多
The aim of this study was to consider the characteristics of intramuscular diffusion status of risperidone and aripiprazole long acting injectable (LAI) by ultrasonography. Subjects were 40 adult subjects diagnosed wi...The aim of this study was to consider the characteristics of intramuscular diffusion status of risperidone and aripiprazole long acting injectable (LAI) by ultrasonography. Subjects were 40 adult subjects diagnosed with schizophrenia and treated with LAI [32 patients were risperidone LAI (RLAI) and 8 patients were aripiprazole LAI (ALAI)]. However, in this paper, only three cases (one RLAI case and 2 ALAI cases) were selected to illustrate the diffusion effects of both LAI. Dorsogluteal intramuscular (IM) injection sites were measured at prone position using the “double cross” method. Before LAI injection, the distance from the epidermis to the under-fascia (DEUF), and distance from the epidermis to the iliac bone (DEI) at the IM injection site were assessed by using ultrasonography: 1) the injection needle was inserted to the gluteus medius, and 2) observed the diffusion status within the muscle injected RLAI and ALAI were confirmed using the B-mode ultrasonography. Both RLAI and ALAI were depicted as high echogenicity with acoustic shadowing. It was considered that the diffusion states of LAIs by ultrasonography were important time course evaluations providing objective evidence.展开更多
文摘BACKGROUND Pyoderma gangrenosum(PG)is one of the most severe extra-intestinal manifest-ations of ulcerative colitis(UC).The treatment of refractory UC combined with PG is challenging,particularly for patients with schizophrenia(SCZ)with a long-term history of risperidone use,and there have been no successfully treated patients reported in the literature.CASE SUMMARY A 36-year-old woman attended the gastroenterological clinic due to intermittent symptoms of diarrhea and mucous bloody stools.Prior to the emergence of these symptoms,the patient had a history of SCZ for 3 years.She had been receiving long-term risperidone treatment and had stable mental symptoms.In April 2023,she was diagnosed with UC E3 moderate and began taking mesalazine 3 g/day.In March 2024,her intestinal symptoms recurred and approximately 2 months later,PG developed in both lower limbs.Previous treatments with adalimumab and steroids were ineffective for PG and UC,and simultaneously,the patient experienced headache,confusion,and severe sleep disturbances.After switching to upadacitinib(UPA)45 mg/day,PG lesions showed complete healing and fecal calprotectin was<10μg/g after 7 weeks of treatment.Following approximately 12 weeks of UPA therapy,colonoscopy indicated that the patient had achieved mucosal healing.No adverse events occurred during UPA induction and main-tenance therapy for 6 months with risperidone.CONCLUSION UPA treatment led to successful resolution of both intestinal and extra-intestinal manifestations in this patient with new-onset UC who had a history of SCZ.No adverse effects were observed with concurrent UPA and risperidone use.
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.
基金Science and Technology Million Project of Inner Mongolia Medical University(Grant No.YKD2014KJBW012)
文摘In the present study, we investigated the complexation of risperidone with hydroxypropyl-β-cyclodextrin （HP-β-CD） in aqueous solution due to the poor water solubility and low oral bioavailability of risperidone in humans. The effect of temperature on the complexation was examined, and thermodynamic parameters of the complexation process, such as Gibbs free energy change （AG）, enthalpy change （AH） and entropy change （AS）, were also explored. Meantime, the solid dispersion of risperidone with HP-β-CD was prepared and confirmed by Fourier IR spectroscopy and X-ray diffractometry. The experimental results suggested that the complex of the drug with HP-β-CD at a molar ratio of 1：1 could form in aqueous solution, and the complexation was an endothermic and entropy-driven process. The risperidone-HP-β-CD solid dispersion exhibited a remarkable improvement in the dissolution rate of the drug. This might be attributed to the amorphous state, the enhanced wettability as well as the complex formation of the drug with HP-β-CD in aqueous solution.
基金supported by thegrant of Stanley Medical Research Institute(No.02I-005),USA
文摘Objective To identify whether sarsasapogenin, a sapogenin from the Chinese medicinal herb Anemarrhena Asphodeloides Bunge, would augment the efficacy of risperidone and significantly improve cognitive functions in patients with negative symptoms dominated schizophrenia. Methods The trial was a double-blind, placebo-controlled, parallel- group design. The eligible patients were randomized into 2 treatment groups： sarsasapogenin group （sarsasapogenin plus risperidone for 8 weeks, n = 41） and placebo group （risperidone only for 8 weeks, n = 39）. At the baseline, as well as at weeks 2, 4 and 8 of treatment, the therapeutic response was measured by using scales including Positive and Nega- tive Symptoms Scale （PANSS）, Wechsler Memory Scale （WMS）, modified Chinese Wechsler Adult Intelligence Scale （mWAIS）, Clinical Global Impression （CGI） and Brief Psychiatry Rating Scale （BPRS）. The study period for each subject was 8 weeks and duration of overall trial was 2 years. Results Patients treated with sarsasapogenin plus risperidone demonstrated no statistically significant differences in changes in PANSS, WMS or mWAIS score at the end-point of the trial compared with patients treated with placebo plus risperidone. The incidence of treatment-emergent adverse events in patients treated with sarsasapogenin was not different from that observed in placebo group. Conclusion Sarsasapogenin did not augment the efficacy of risperidone in treating negative symptoms dominated schizophrenia. Sarsasapogenin at a dosage of 200 mg per day added to a flexible dosage of risperidone at 2-4 mg per day is safe and well tolerated by patients with negative symptoms dominated schizophrenia.
文摘Aim To investigate the NMR spectroscopy of amlodipine and risperidone.Methods 1D NMR and 2D NMR experimental techniques of gCOSY, gHSQC and gHMBC were wsed. Results Theassignments of the ~1H and ^(13) C NMR data for the two drugs were performed and confirmed by theevidence of J_(HF) and J_(CF). Conclusion The structures of amlodipine and risperidone wereconfirmed by careful analysis of regular 1D and 2D NMR spectroscopy.
基金Supported by Shanghai Civil Administration Bureau,No.8-2-50.
文摘BACKGROUND Prior studies have noted great variability in the plasma levels of risperidone(RIS).Plasma concentrations of RIS and its active moiety are highly variable and depend on absorption,metabolism,and other predictors of metabolic dysregulation;however,these factors are poorly understood and the association between metabolic change and change in psychopathology is uncertain.AIM To ascertain the characteristics of chronic schizophrenic patients treated with RIS,and to assess their relationship with plasma RIS levels.METHODS This was a descriptive cross-sectional study of 50 patients with a diagnosis of schizophrenic psychosis treated with RIS in a psychiatric service.The plasma concentrations of RIS and its metabolite 9-hydroxyrisperidone were determined by high performance liquid chromatography.The patients’demographic and clinical characteristics,and psychopathologies were assessed,and the associations between clinical variables and plasma levels of RIS were explored.RESULTS Male patients received higher doses of RIS than female ones,but plasma concentrations of RIS and risperidone+9-hydroxyrisperidone(active moiety)were higher in female patients.Age and the mean scores of the general psychopathology subscale of the Positive and Negative Syndrome Scale(PANSS)were significantly positively correlated with plasma concentrations of risperidone+9-hydroxyrisperidone adjusted for weight and dose in all 50 subjects.In male subjects,we found a statistically significant positive correlation between the concentrations of risperidone+9-hydroxyrisperidone in plasma/(dose×kg)and age,mean PANSS negative subscale scores,mean PANSS general psychopathology subscale scores,and mean PANSS total scores.CONCLUSION Long-term use of RIS should be closely monitored in older patients and females to minimize the risk of high concentrations which could induce side effects.
基金Foundation items:The National Major Scientific and Technological Special Project for"Significant New Drug Development"during the Twelfth Five-year Planning Period of China(Grant No.2014ZX09303303).
文摘In the present study,we aimed to determine the pharmacokinetics(PK),pharmacodynamics(PD),adverse events(AEs),and their relationships in Chinese patients with schizophrenia after a single dose of long-acting risperidone.Schizophrenic patients(six females and seven males)were enrolled in this study.Serial blood samples were collected after drug administration during 63 d,and the drug concentrations were analyzed by LC-MS/MS.Safety and tolerance were evaluated by monitoring the AEs,changes in clinical laboratory results,12-lead ECG,vital signs,physical examination,and injection-site reactions.The extrapyramidal symptoms were evaluated using the ESRS.Efficacy was evaluated by the PANSS and BPRS.Twelve out of the 13 participants completed the trial.There were few clinically meaningful changes in mean clinical laboratory values,vital signs,or ECG parameters,except for the prolactin level and body weight.There were no serious AEs,and those observed were reversible.Significant clinical improvements in PANSS and PANSS-derived BPRS total scores were observed.The mean(standard deviation,coefficient of variation)values for these PK parameters were as follows:C_(max),8.954(8.059,90.0%)ng/mL;area under the curve AUC_(0-t),2453(1156,47.1%)ng·h/mL;AUC_(0-∞),2472(1160,46.9%)ng·h/mL;t_(max),830.0(min:744.0,max:984.0,11.8%)h;and t_(1/2),68.56(10.77,15.7%)h.The PK characteristics of long-acting risperidone showed a high level of inter-individual variation,while there were no clear correlations between PK,efficacy and AEs among the patients in the present study.
文摘This study presents a rapid, specific and sensitive liquid chromatography/tandem mass spectrometry (LC-MS/MS) assay for determination of risperidone (RIS) in human serum using paroxetine as an internal standard (IS). An Alltima-C18 column (2.1 mm×100 mm, 3 μm) and a mobile phase consisting of 0.1% formic acid-acetonitrile (40:60, v/v) were used for separation. The analysis was performed by selected reaction monitoring (SRM) method, and the peak area of the m/z 411.3→191.1 transition for RIS was measured versus that of the m/z 330.1→192.1 transition for IS to generate the standard curves. The assay linearity of RIS was confirmed over the range 0.25～50.00 ng/ml and the limit of quantitation was 0.05 ng/ml. The linear range corresponds well with the serum concentrations of the analytes obtained in clinical pharmacokinetic studies. Intraday and interday relative standard deviations were 1.85%～9.09% and 1.56%～4.38%, respectively. The recovery of RIS from serum was in the range of 70.20%～84.50%. The method was successfully applied to investigate the bioequivalence between two kinds of tablets (test versus reference products) in 18 healthy male Chinese volunteers. The result suggests that two formulations are bioequivalent.
基金supported by the project of Science Fund for Creative Research Groups of the National Natural Science Foundation of China(81221002)Rational Medication Application Patterns of Schizophrenia(BMU20140430) of Peking University Health Science Center
文摘Dear editor, P-glycoprotein （P-gp, also known as ATP-binding cassette transport sub-family B member 1, ABCB1） is a potent ATP-dependent efflux pump for a wide variety of drugs. Although studies of its substrates are abundant [ 1, 2], and ABCB1 is a well-conserved gene, there is increasing evi- dence that its polymorphisms affect substrate specificity [3]. A previous study reported that the synonymous single nucleotide polymorphism （SNP） C3435T （rs1045642） affects the timing of co-translational folding and insertionof P-gp into the membrane,
文摘Objectives: Testing a hypothesis, that platelet cytochrome c-oxidase (COX) activities in patients with paranoid schizophrenia, acute episode, may be linked to dynamics of their clinical patterns and quality of cognitive functioning under antipsychotic treatment. Methods: Psychopatho-logical (PANSS, NSA-16) and cognitive assess-ments;platelet COX enzymatic activity determination, post-hoc nonparametric statistical analysis. Results: Psychopathological and cognitive assessments were done and blood was sampled in patients before (at baseline) and after treatment with risperidone. Following regu- larities were found after the treatment of patients: Significant elevation of COX, wherein the higher was COX at baseline, the more prominent was decrease in PANSSneg and NSA rates;significant negative correlation between COX and executive time in cognitive tests. When the patient group was divided by median of COX at baseline into two subgroups (greater or equal median, and 20% was assigned to the first subgroup;significantly larger amount of patients with PANSSneg by <20% was assigned to the second group. Conclusions: Therapy with risperidone seems to be more effective for patients with higher COX activity at baseline, but this fact requires further study.
文摘Objective: To explore the different effects of paliperidone and risperidone therapy on blood lipid and Hcy metabolism as well as endocrine hormones in patients with schizophrenia. Methods: A total of 118 patients with schizophrenia who were treated in the hospital between December 2014 and February 2017 were collected as the research subjects and divided into control group and study group by random number table, each group with 59 cases. Control group received risperidone therapy, observation group received paliperidone therapy, and the differences in the levels of blood lipid indexes, Hcy metabolism indexes and endocrine hormones were compared between the two groups before and after treatment. Results:There was no statistically significant difference in the levels of blood lipid indexes, Hcy and endocrine hormones between the two groups before treatment. After treatment, lipid indexes TG and TC levels in peripheral blood of study group were lower than those of control group while HDL-C content was higher than that of control group;Hcy level in serum of study group was lower than that of control group;endocrine hormones FT3, FT4, T and E2 levels in serum of study group were higher than those of control group. Conclusion: paliperidone therapy for schizophrenia can be more effective than risperidone in regulating blood lipid metabolism, Hcy metabolism and endocrine hormones.
基金the National Natural Science Foundation of China (No.81471358)Shanghai Health and Family Planning Commission Youth Fund Project (No.20144Y0080)+4 种基金Shanghai Health and Family Planning Commission Youth Fund Project (No.20154Y0045)Shanghai Health and Family Planning Commission Fund Project (No.201740089)Shanghai Natural Science Foundation(15ZR1435300)Shanghai JiaoTong University School of Medicine Natural Science and Technology Foundation(14XJ10080)the Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support (No.20152530).
文摘Background Risperidone (RSP) has a rapid onset in vivo, low dosage and high plasma protein binding rate, therefore therapeutic drug monitoring (TDM) is needed to ensure safety in clinical treatment. However, compared with blood, hair is non-invasive, safe, non-infectious and easy to transport and store. Aims This study aims to investigate the correlations among the drug concentrations of RSP in hair and serum, which provides an experimental basis to explore hair as a novel biomaterial to meet the needs of clinical detection. Methods 34 patients with schizophrenia treated with RSP for more than 3 months were enrolled in this study. About 1 cm section of hair near the scalp was taken from the subjects, pretreated and detected by liquid chromatography-mass spectrometry. A correlation analysis was conducted among the drug concentrations in hair, the serum concentrations and the daily dosage. The data were analysed usi叩 SPSS 20.0 software. Results There was significant correlation between the hair concentration of RSP (two-tailed test, r=0.440, p=0.009) with the serum concentration of RSP, and the hair concentration of 9-hydroxyrisperidone (9-HR) with the serum concentration of 9-HR had no significant correlation (two-tailed test, r=-0.217, p=0.217);the total concentration of the RSP and 9-HR had no significant correlation between hair and serum (r=0.227, p=0.196). The dosage had no statistically significant correlation with the concentration of RSP in hair (r=0.207, p=0.241), 9-HR in hair (r=-0.194, p=0.271) and the total concentration of RSP and 9-HR in hair (r=0.188, p=0.288). There was no statistical correlation between the dosage and the concentration of RSP in serum (r=-0.059, p=0.741), but significant correlation between the dosage and 9-HR in serum (r=0.581 p<0.001) was found, and the correlation between the dosage and the total concentration of the two drugs RSP and 9-HR in serum was also significant (r=0.437, p=0.01). Conclusion The correlation analysis showed that the concentration of RSP in hair was statistically significant with the serum RSP concentration. In this study, we provided some experimental basis for hair as a new biomaterial to monitor the therapeutic drug concentration.
文摘Inter-individual variability in oral drug efficacy and toxicity is commonly observed in all therapeutic areas.Importantly,interindividual variability in drug uptake and metabolism can result in poor drug response,adverse drug reactions,or unfavorable drug–drug interaction.One of the common causes of individual variations in drug response is genetic variation of drug transporters and metabolizing enzymes[1,2].We focus on the interplay between efflux transporter(ATP-binding cassette,subfamily B(MDR/TAP),member 1/ABCB1)and cytochrome P450s according to genetic polymorphism[3].The objective of this lecture is to investigate the combined influence of genetic polymorphisms in ABCB1 and CYP2D6 genes on risperidone pharmacokinetics[4].
文摘Risperidone long-acting injectable (RLAI) is approved for the treatment of schizophrenia in many countries. The suggested site is the gluteal muscle with a needle length of two inches (50 mm) in Japan, which is longer than the ordinarily used needle for intramuscular injections. The aim of this study was to determine the optimal needle insertion length for accurate delivery of RLAI procedure among subjects who have normal body mass index (BMI: 18 to 25) and high BMI (>25). Thirty-seven patients with schizophrenia were administered RLAI intramuscularly into the dorsogluteal muscle. The standard procedure required inserting 80% of the two inch needle. By using data collected by ultrasonography, the findings confirmed that the median needle insertion lengths for subjects with normal and high BMI were 39.0 and 45.5 mm, respectively. To deliver RLAI effectively and safely, the authors strongly recommend that a specialized needle be used that is “marked” at the 40 mm point from the tip of the needle to the base. In this way regardless of subcutaneous fat content, the RLAI can be safely delivered into the muscle without causing untoward or side effects.
基金National Natural Scicnce Foundation of China(No.81973747,81873299)。
文摘Objective:The efficacy and occurrence of adverse reactions of prescriptions containing phlegm-resolving Chinese medicine combined with risperidone in the treatment of schizophrenia were retrospectively studied by means of meta-analysis.Methods:A variety of different Chinese and English databases were searched from January 1,2000 to May 1,2020.Review Manager 5.3 software was used to evaluate the methodological quality of the included studies.The positive and negative symptom scale(PANSS)was used as the evaluation standard to analyze the total scores,positive scores,negative scores and general psychopathological scores,clinical efficacy and safety of prescriptions containing phlegmresolving Chinese medicine combined with risperidone of schizophrenia.The heterogeneity test and sensitivity analysis were also carried out by Review Manager 5.3,and the potential publication bias was analyzed by"funnel plot".Results:A total of 1515 patients were included in 15 studies.Compared with control group of risperidone alone,the total PANSS scale score,positive symptom score,negative symptom score and general psychopathological score of the treatment group of phlegm-resolving Chinese medicine combined with risperidone were all lower than those of the control group(P=0.01,MD=-6.35,95%CI[-11.29,-1.40]),(P=0.04,MD=-1.42,95%CI[-2.74,-0.09]),(P<0.01,MD=-2.16,95%CI[-3.41,-0.91]),and(P<0.01,MD=-3.80,95%CI[-6.37,-1.24]),the clinical efficacy of phlegm-resolving Chinese medicine combined with risperidone treatment group on schizophrenia was better than that of the control group[P<0.01,RR=1.09,95%CI(1.05-1.13)].The incidence of adverse reactions was reduced(P=0.02,RR=0.56,95%CI[0.34-0.93]).Conclusion:The combination of prescriptions containing phlegm-resolving Chinese medicine and risperidone can effectively improve the efficacy of patients with schizophrenia and reduce the occurrence of adverse drug reactions compared with risperidone alone.
文摘Brain developmental disorders in humans, including Autism Spectrum Disorders (ASD) and Down’s syndrome, have been linked to increased serotonin levels. This work was designed to study changes in serotonin levels in the early stages of development with two classes of antipsychotic drugs: Risperidone, a drug that blocks serotonin and dopamine receptors, and fluoxetine, a serotonin reuptake inhibitor. The use of antipsychotic drugs is a solid choice to study the decrease and increase of these neurotransmitters and their influence on development. The study of these parameters will give an idea of the effects of serotonin in early developmental stages. To this end, we examined the effects of risperidone and fluoxetine on the locomotor activity, heart rate and brain development of zebrafish larvae. Our results showed that in larvae exposed to fluoxetine alone, swimming was significantly increased at 9 dpf (days post-fertilization). Erratic and abnormal movements were observed suggesting a toxic effect of fluoxetine. No erratic swimming was observed in larvae treated with fluoxetine plus risperidone. Both drugs presented morphological changes in dopaminergic neurons and mononeurons. Exposure to fluoxetine plus risperidone indicated possible reversal effects. Studies in zebrafish allow obtaining new insights into the side effects of these drugs as well as into the brain control of locomotor activity. Testing several drug-induced changes in behavior and serotonin levels is one of the experimental approaches for screening a new therapeutically relevant compound, and thus, merits further research.
文摘We present the case of a 24-year-old man, who was a keen runner, developing chronic bilateral lower leg compartment syndrome following co-administration of Risperidone and Sodium Valproate. Having had failed medical and physical therapies, he underwent surgical decompression of his more problematic left lower leg compartments. In the interval between sequential fasciotomies, control of his psychiatric symptoms allowed the dose of his Risperidone to be reduced, resulting in a greater exercise tolerance. Ultimately he no longer required the contra-lateral lower leg compartments to be decompressed surgically. He had returned to his original level of activity with no further psychotic episodes.
文摘The aim of this study was to consider the characteristics of intramuscular diffusion status of risperidone and aripiprazole long acting injectable (LAI) by ultrasonography. Subjects were 40 adult subjects diagnosed with schizophrenia and treated with LAI [32 patients were risperidone LAI (RLAI) and 8 patients were aripiprazole LAI (ALAI)]. However, in this paper, only three cases (one RLAI case and 2 ALAI cases) were selected to illustrate the diffusion effects of both LAI. Dorsogluteal intramuscular (IM) injection sites were measured at prone position using the “double cross” method. Before LAI injection, the distance from the epidermis to the under-fascia (DEUF), and distance from the epidermis to the iliac bone (DEI) at the IM injection site were assessed by using ultrasonography: 1) the injection needle was inserted to the gluteus medius, and 2) observed the diffusion status within the muscle injected RLAI and ALAI were confirmed using the B-mode ultrasonography. Both RLAI and ALAI were depicted as high echogenicity with acoustic shadowing. It was considered that the diffusion states of LAIs by ultrasonography were important time course evaluations providing objective evidence.
