Introduction Fexofenadine, the primary metabolite of terfenadine, is a selective and peripherally acting Hl receptor antagonist and has been developed as a non-sedating H1 antihistaminic drug. In clinical studies, it ...Introduction Fexofenadine, the primary metabolite of terfenadine, is a selective and peripherally acting Hl receptor antagonist and has been developed as a non-sedating H1 antihistaminic drug. In clinical studies, it is used for the treatment of seasonal allergic rhinitis and chronic urticaria without producing sedation.展开更多
This study presented a simple, rapid, and sensitive liquid chromatography analytical method employing tandem mass spectrometry （LC-MS/MS） to determine fexofenadine in human plasma. After the de-proteination procedur...This study presented a simple, rapid, and sensitive liquid chromatography analytical method employing tandem mass spectrometry （LC-MS/MS） to determine fexofenadine in human plasma. After the de-proteination procedure with acetonitrile, chromatographic separation of fexofenadine was performed using a reversed-phase Eclipse XDB-C8 column with a mobile phase consisted of 1 mmol/L ammonium acetate buffer solution containing 0.2% formic acid-methanol （45：55, v/v）. Fexofenadine was quantified using tandem mass detection in the electrospray ionization （ESI） positive ion mode. The flow rate of the mobile phase was 1 mL/min, and the retention times of fexofenadine and the internal standard （IS, losartan） were 1.76 min and 2.65 min, respectively. The calibration curve was linear over the plasma concentration range of 1-1000 ng/mL. The relative standard deviations of intra- and inter-batches were less than 10.4% and 15.4%, respectively. The LC-MS/MS method reported in this study showed higher sensitivity for the quantification of fexofenadine in human plasma than that shown by previously described analytical methods. Lastly, the method was successfully applied to the pharmacokinetic of fexofenadine in healthy Taiwan volunteers.展开更多
Aim: To investigate the role of fexofenadine, a mast cell blocker, on semen quality in the treatment of infertile men. Methods: The study included 16 Turkish idiopathic infertile men with azoospermia or oligozoospermi...Aim: To investigate the role of fexofenadine, a mast cell blocker, on semen quality in the treatment of infertile men. Methods: The study included 16 Turkish idiopathic infertile men with azoospermia or oligozoospermia who underwent testicular biopsy to examine mast cells containing tryptase. In all patients, a complete medical history, clinical examination, semen analysis and serum hormone assay were carried out. The biopsy specimens were immunohistochemically stained with antihuman tryptase for mast cells. The number of total mast cells per seminiferous tubule was calculated and recorded as mast cell index. The patients were divided into two groups according to their mast cell index: the higher (≥1, n=9) and the lower (<1, n=7) index groups. Fexofenadine was administered orally at a dose of 180 mg/day for 4 to 9 months. Pre-and post-treatment semen parameters, including total motile sperm counts (TMC) were recorded and compared. Spontaneous pregnancies after the treatment were registered. Results: There was no statistically significant difference in TMC between the pre-treatment and post-treatment values in patients with higher and lower mast cell index (P≥0.05). In both groups, nobody had a significant response to the treatment and there was no spontaneous pregnancy after the treatment. Conclusion: Although testicular dysfunction is closely associated with increased number of testicular mast cells, fexofenadine, a mast cell blocker, appears not having any benefit in the treatment of Turkish infertile men with a significant increase in testicular mast cells. (Asian J Androl 2002 Dec; 4: 291-294)展开更多
Fexofenadine is useful in various allergic disease treatment.However,the pharmacokinetic variability information and quantitative factor identification of fexofenadine are very lacking.This study aimed to verify the v...Fexofenadine is useful in various allergic disease treatment.However,the pharmacokinetic variability information and quantitative factor identification of fexofenadine are very lacking.This study aimed to verify the validity of previously proposed genetic factors through fexofenadine population pharmacokinetic modeling and to explore the quantitative correlations affecting the pharmacokinetic variability.Polymorphisms of the organic-anion-transporting-polypeptide(OATP)1B1 and 2B1 have been proposed to be closely related to fexofenadine pharmacokinetic diversity.Therefore,modeling was performed using fexofenadine oral exposure data according to the OATP1B1-and 2B1-polymorphisms.OATP1B1 and 2B1 were identified as effective covariates of clearance(CL/F)and distribution volume(V/F)-CL/F,respectively,in fexofenadine pharmacokinetic variability.CL/F and average steady-state plasma concentration of fexofenadine differed by up to 2.17-and 2.20-folds,respectively,depending on the OATP1B1 polymorphism.Among the individuals with different OATP2B1 polymorphisms,the CL/F and V/F differed by up to 1.73-and 2.00-folds,respectively.Ratio of the areas under the curves following single-and multiple-administrations,and the cumulative ratio were significantly different between OATP1B1-and 2B1-polymorphism groups.Based on quantitative prediction comparison through a model-based approach,OATP1B1 was confirmed to be relatively more important than 2B1 regarding the degree of effect on fexofenadine pharmacokinetic variability.Based on the established pharmacokineticpharmacodynamic relationship,the difference in fexofenadine efficacy according to genetic polymorphisms of OATP1B1 and 2B1 was 1.25-and 0.87-times,respectively,and genetic consideration of OATP1B1 was expected to be important in the pharmacodynamics area as well.This population pharmacometrics study will be a very useful starting point for fexofenadine precision medicine.展开更多
A rapid and sensitive liquid chromatography-tandem mass spectrometry method（LC-MS/MS）was developed and validated for the quantification of fexofenadine in human plasma,to conduct comparative bioavailability studies....A rapid and sensitive liquid chromatography-tandem mass spectrometry method（LC-MS/MS）was developed and validated for the quantification of fexofenadine in human plasma,to conduct comparative bioavailability studies.Human plasma was extracted with a mixture of dichloromethane-diethyl ether（volume ratio 2∶3）in a basic environment and the extract was separated on a C18 column with a mobile phase consisting of acetonitrile-methanol-10 mmol/L ammonium acetate（volume ratio 45∶45∶10）.The analytes were detected via electrospray ionization（ESI）tandem mass spectrometry in the multiple-reaction-monitoring（MRM）mode.The linearity was within a range of 1-1000 ng/mL.The intra-and inter-day precision were〈4.1% and〈4.8%,respectively,and the accuracy was in the range of 95.0%-105%.The method was applied to the quantification of fexofenadine human plasma from 20 healthy male Chinese volunteers,according to a single dose,randomized,two-way crossover design with a two-week washout period.The mean values of major pharmacokinetic parameters of ρmax,AUC0-48,AUC0-∞,tmax,and t1/2 were determined from the plasma concentration.The analysis of variance（ANOVA）did not show any significant difference between the two products of fexofenadine and 90% confidence intervals fell within the acceptable range for bioequivalence.展开更多
High-throughput measurements of ciprofloxacin, clomipramine and fexofenadine hydrochlorides were performed by employing an automatic 8-channel electrical titrator. Silver nitrate （AgNO3） and sodium tetraphenylborate...High-throughput measurements of ciprofloxacin, clomipramine and fexofenadine hydrochlorides were performed by employing an automatic 8-channel electrical titrator. Silver nitrate （AgNO3） and sodium tetraphenylborate （NaTPB） were used as titrants. When AgNO3 was used for measuring the drugs in pure form, recoveries were 97.6%-102.0% with RSD values ≤1.0%; for measuring them in pharmaceutical formulations, recoveries were 96.6%-99.1% with RSD values ≤1.0%. Batch samples of eight could be measured simultaneously and maximally 30 measurements per minute could be completed. When NaTPB was used for measuring the drugs in pure form, the recoveries were 96.8%-102.6% with RSD values 〈0.8%; for measuring them in pharmaceutical formulations, the recoveries were 97.5%-102.7% with RSD values ≤0.9%. For all analyses, no auxiliary devices or chemicals were needed and there was no requirement for changing or cleaning working electrodes between measurements. The efficiency, accuracy and precision of the proposed method make it an alternative for routine quality control analyses.展开更多
Objectives: To improve the aqueous solubility and dissolution of fexofenadine HCl, an attempt was made to prepare its fast dissolving tablets by lyophilization technique. Methods: For the preparation of lyophilized ta...Objectives: To improve the aqueous solubility and dissolution of fexofenadine HCl, an attempt was made to prepare its fast dissolving tablets by lyophilization technique. Methods: For the preparation of lyophilized tablets (F1-F32), the drug was dispersed in a hydrated solution of water-soluble polymers (gelatin/maltodextrin/acacia) containing glycine and mannitol. The blend was pelted down into the patches of a blister pack, frozen down and then lyophilized. Different characterization parameters viz. differential scanning calorimetry, hardness, weight variation, X-ray diffraction (XRD), scanning electron microscopy (SEM), mercury porosimetry, solubility, wetting time and water absorption ratio, lyophilization tablet index, drug content, in vitro dissolution and stability were evaluated. Key findings: Tablets (F32) containing acacia were found to have fast disintegration and relatively higher mechanical strength with improved drug solubility. X-ray diffractogram and scanning electron micrograph indicated decrease in crystallinity of drug and a good porous structure property for prepared tablet, respectively. Dissolution study showed complete drug released within 5 min. Moreover, tablets (F32) were found to be stable for one month at 25 ± 2 °C/60 ± 5% relative humidity.展开更多
A rapid, fast and precise method has been developed and validated for the simultaneous determination of amlodipine with H1-receptor antagonists (cetirizine, fexofenadine, and buclizine) from dosage forms. The chromato...A rapid, fast and precise method has been developed and validated for the simultaneous determination of amlodipine with H1-receptor antagonists (cetirizine, fexofenadine, and buclizine) from dosage forms. The chromatography was performed on a Purospher? Star, C18 (5 mm, 250 × 4.6 mm) column using acetonitrile: buffer (0.01 mM) (40:60, v/v, pH adjusted to 3.0), as a mobile phase. The mobile phase was pumped at a flow rate of 1.0 mL·min-1 and UV detection was performed at 240 nm. The method was validated for linearity, accuracy, precision and specificity. The method was applied to study the interaction between amlodipine and H1-receptor antagonists. These interactions were carried out in simulated gastric juice (pH 1), simulated full stomach (pH 4), blood pH (pH 7.4) and simulating GI (pH 9). The interacting drugs were heated at 37℃ with intermit-tent shaking and the samples were withdrawn every thirty minutes for three hours and drug contents were analyzed by RP-HPLC techniques. In most cases the in vitro availability of amlodipine was decreased. It was observed that the change in in vitro availability was pH dependent.展开更多
文摘Introduction Fexofenadine, the primary metabolite of terfenadine, is a selective and peripherally acting Hl receptor antagonist and has been developed as a non-sedating H1 antihistaminic drug. In clinical studies, it is used for the treatment of seasonal allergic rhinitis and chronic urticaria without producing sedation.
文摘This study presented a simple, rapid, and sensitive liquid chromatography analytical method employing tandem mass spectrometry （LC-MS/MS） to determine fexofenadine in human plasma. After the de-proteination procedure with acetonitrile, chromatographic separation of fexofenadine was performed using a reversed-phase Eclipse XDB-C8 column with a mobile phase consisted of 1 mmol/L ammonium acetate buffer solution containing 0.2% formic acid-methanol （45：55, v/v）. Fexofenadine was quantified using tandem mass detection in the electrospray ionization （ESI） positive ion mode. The flow rate of the mobile phase was 1 mL/min, and the retention times of fexofenadine and the internal standard （IS, losartan） were 1.76 min and 2.65 min, respectively. The calibration curve was linear over the plasma concentration range of 1-1000 ng/mL. The relative standard deviations of intra- and inter-batches were less than 10.4% and 15.4%, respectively. The LC-MS/MS method reported in this study showed higher sensitivity for the quantification of fexofenadine in human plasma than that shown by previously described analytical methods. Lastly, the method was successfully applied to the pharmacokinetic of fexofenadine in healthy Taiwan volunteers.
文摘Aim: To investigate the role of fexofenadine, a mast cell blocker, on semen quality in the treatment of infertile men. Methods: The study included 16 Turkish idiopathic infertile men with azoospermia or oligozoospermia who underwent testicular biopsy to examine mast cells containing tryptase. In all patients, a complete medical history, clinical examination, semen analysis and serum hormone assay were carried out. The biopsy specimens were immunohistochemically stained with antihuman tryptase for mast cells. The number of total mast cells per seminiferous tubule was calculated and recorded as mast cell index. The patients were divided into two groups according to their mast cell index: the higher (≥1, n=9) and the lower (<1, n=7) index groups. Fexofenadine was administered orally at a dose of 180 mg/day for 4 to 9 months. Pre-and post-treatment semen parameters, including total motile sperm counts (TMC) were recorded and compared. Spontaneous pregnancies after the treatment were registered. Results: There was no statistically significant difference in TMC between the pre-treatment and post-treatment values in patients with higher and lower mast cell index (P≥0.05). In both groups, nobody had a significant response to the treatment and there was no spontaneous pregnancy after the treatment. Conclusion: Although testicular dysfunction is closely associated with increased number of testicular mast cells, fexofenadine, a mast cell blocker, appears not having any benefit in the treatment of Turkish infertile men with a significant increase in testicular mast cells. (Asian J Androl 2002 Dec; 4: 291-294)
文摘Fexofenadine is useful in various allergic disease treatment.However,the pharmacokinetic variability information and quantitative factor identification of fexofenadine are very lacking.This study aimed to verify the validity of previously proposed genetic factors through fexofenadine population pharmacokinetic modeling and to explore the quantitative correlations affecting the pharmacokinetic variability.Polymorphisms of the organic-anion-transporting-polypeptide(OATP)1B1 and 2B1 have been proposed to be closely related to fexofenadine pharmacokinetic diversity.Therefore,modeling was performed using fexofenadine oral exposure data according to the OATP1B1-and 2B1-polymorphisms.OATP1B1 and 2B1 were identified as effective covariates of clearance(CL/F)and distribution volume(V/F)-CL/F,respectively,in fexofenadine pharmacokinetic variability.CL/F and average steady-state plasma concentration of fexofenadine differed by up to 2.17-and 2.20-folds,respectively,depending on the OATP1B1 polymorphism.Among the individuals with different OATP2B1 polymorphisms,the CL/F and V/F differed by up to 1.73-and 2.00-folds,respectively.Ratio of the areas under the curves following single-and multiple-administrations,and the cumulative ratio were significantly different between OATP1B1-and 2B1-polymorphism groups.Based on quantitative prediction comparison through a model-based approach,OATP1B1 was confirmed to be relatively more important than 2B1 regarding the degree of effect on fexofenadine pharmacokinetic variability.Based on the established pharmacokineticpharmacodynamic relationship,the difference in fexofenadine efficacy according to genetic polymorphisms of OATP1B1 and 2B1 was 1.25-and 0.87-times,respectively,and genetic consideration of OATP1B1 was expected to be important in the pharmacodynamics area as well.This population pharmacometrics study will be a very useful starting point for fexofenadine precision medicine.
文摘A rapid and sensitive liquid chromatography-tandem mass spectrometry method（LC-MS/MS）was developed and validated for the quantification of fexofenadine in human plasma,to conduct comparative bioavailability studies.Human plasma was extracted with a mixture of dichloromethane-diethyl ether（volume ratio 2∶3）in a basic environment and the extract was separated on a C18 column with a mobile phase consisting of acetonitrile-methanol-10 mmol/L ammonium acetate（volume ratio 45∶45∶10）.The analytes were detected via electrospray ionization（ESI）tandem mass spectrometry in the multiple-reaction-monitoring（MRM）mode.The linearity was within a range of 1-1000 ng/mL.The intra-and inter-day precision were〈4.1% and〈4.8%,respectively,and the accuracy was in the range of 95.0%-105%.The method was applied to the quantification of fexofenadine human plasma from 20 healthy male Chinese volunteers,according to a single dose,randomized,two-way crossover design with a two-week washout period.The mean values of major pharmacokinetic parameters of ρmax,AUC0-48,AUC0-∞,tmax,and t1/2 were determined from the plasma concentration.The analysis of variance（ANOVA）did not show any significant difference between the two products of fexofenadine and 90% confidence intervals fell within the acceptable range for bioequivalence.
基金supported by Special Scientific Research Funds for Central Non-profit Institutes,Yellow Sea Fisheries Research Institute,Chinese Academy of Fishery Sciences(YSFRI-CAFS)(No.20603022016003)Import of International Advanced Agricultural Science and Technology Plan(948 Project)of Chinese Ministry of Agriculture(No.2016-X28)+2 种基金Central Public Interest Scientific Institution Basal Research Fund,CAFS(No.2016RC-BR02)Qingdao National Laboratory for Marine Science and Technology(No.2015ASKJ02-05)Key R&D Program of Shandong Province(No.2016GSF120008)
文摘High-throughput measurements of ciprofloxacin, clomipramine and fexofenadine hydrochlorides were performed by employing an automatic 8-channel electrical titrator. Silver nitrate （AgNO3） and sodium tetraphenylborate （NaTPB） were used as titrants. When AgNO3 was used for measuring the drugs in pure form, recoveries were 97.6%-102.0% with RSD values ≤1.0%; for measuring them in pharmaceutical formulations, recoveries were 96.6%-99.1% with RSD values ≤1.0%. Batch samples of eight could be measured simultaneously and maximally 30 measurements per minute could be completed. When NaTPB was used for measuring the drugs in pure form, the recoveries were 96.8%-102.6% with RSD values 〈0.8%; for measuring them in pharmaceutical formulations, the recoveries were 97.5%-102.7% with RSD values ≤0.9%. For all analyses, no auxiliary devices or chemicals were needed and there was no requirement for changing or cleaning working electrodes between measurements. The efficiency, accuracy and precision of the proposed method make it an alternative for routine quality control analyses.
文摘Objectives: To improve the aqueous solubility and dissolution of fexofenadine HCl, an attempt was made to prepare its fast dissolving tablets by lyophilization technique. Methods: For the preparation of lyophilized tablets (F1-F32), the drug was dispersed in a hydrated solution of water-soluble polymers (gelatin/maltodextrin/acacia) containing glycine and mannitol. The blend was pelted down into the patches of a blister pack, frozen down and then lyophilized. Different characterization parameters viz. differential scanning calorimetry, hardness, weight variation, X-ray diffraction (XRD), scanning electron microscopy (SEM), mercury porosimetry, solubility, wetting time and water absorption ratio, lyophilization tablet index, drug content, in vitro dissolution and stability were evaluated. Key findings: Tablets (F32) containing acacia were found to have fast disintegration and relatively higher mechanical strength with improved drug solubility. X-ray diffractogram and scanning electron micrograph indicated decrease in crystallinity of drug and a good porous structure property for prepared tablet, respectively. Dissolution study showed complete drug released within 5 min. Moreover, tablets (F32) were found to be stable for one month at 25 ± 2 °C/60 ± 5% relative humidity.
文摘A rapid, fast and precise method has been developed and validated for the simultaneous determination of amlodipine with H1-receptor antagonists (cetirizine, fexofenadine, and buclizine) from dosage forms. The chromatography was performed on a Purospher? Star, C18 (5 mm, 250 × 4.6 mm) column using acetonitrile: buffer (0.01 mM) (40:60, v/v, pH adjusted to 3.0), as a mobile phase. The mobile phase was pumped at a flow rate of 1.0 mL·min-1 and UV detection was performed at 240 nm. The method was validated for linearity, accuracy, precision and specificity. The method was applied to study the interaction between amlodipine and H1-receptor antagonists. These interactions were carried out in simulated gastric juice (pH 1), simulated full stomach (pH 4), blood pH (pH 7.4) and simulating GI (pH 9). The interacting drugs were heated at 37℃ with intermit-tent shaking and the samples were withdrawn every thirty minutes for three hours and drug contents were analyzed by RP-HPLC techniques. In most cases the in vitro availability of amlodipine was decreased. It was observed that the change in in vitro availability was pH dependent.
