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
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
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
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
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
Many reviewers have contributed their expertise and time to the peer review, a critical process to ensure the quality of World Journal of Gastrointestinal
Many reviewers have contributed their expertise and time to the peer review,a critical process to ensure the quality of World Journal of Gastrointestinal
We acknowledge our sincere thanks to our reviewers. Many reviewers have contributed their expertise and time to the peer review, a critical process to ensure the quality of our World Series Journals. Both the editors ...We acknowledge our sincere thanks to our reviewers. Many reviewers have contributed their expertise and time to the peer review, a critical process to ensure the quality of our World Series Journals. Both the editors of the journals and authors of the manuscripts submitted to the journals are grateful to the following reviewers展开更多
Many reviewers have contributed their expertise and time to the peer review, a critical process to ensure the quality of World Journal of Gastrointestinal Pharmacology and Therapeutics. The editors
We acknowledge our sincere thanks to our reviewers.Many reviewers have contributed their expertise and time to the peer review,a critical process to ensure the quality of our World Series Journals.Both the editors of ...We acknowledge our sincere thanks to our reviewers.Many reviewers have contributed their expertise and time to the peer review,a critical process to ensure the quality of our World Series Journals.Both the editors of the journals and authors of the manuscripts submitted to the journals are grateful to the following reviewers for reviewing the articles(either published or rejected) over the past period of time.展开更多
Many reviewers have contributed their expertise and time to the peer review,a critical process to ensure the quality of World Journal of Gastrointestinal Pharmacology and Therapeutics.The editors and authors of the ar...Many reviewers have contributed their expertise and time to the peer review,a critical process to ensure the quality of World Journal of Gastrointestinal Pharmacology and Therapeutics.The editors and authors of the articles submitted to the journal are grateful to the展开更多
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.
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Many reviewers have contributed their expertise and time to the peer review, a critical process to ensure the quality of World Journal of Gastrointestinal
文摘Many reviewers have contributed their expertise and time to the peer review,a critical process to ensure the quality of World Journal of Gastrointestinal
文摘We acknowledge our sincere thanks to our reviewers. Many reviewers have contributed their expertise and time to the peer review, a critical process to ensure the quality of our World Series Journals. Both the editors of the journals and authors of the manuscripts submitted to the journals are grateful to the following reviewers
文摘Many reviewers have contributed their expertise and time to the peer review, a critical process to ensure the quality of World Journal of Gastrointestinal Pharmacology and Therapeutics. The editors
文摘We acknowledge our sincere thanks to our reviewers.Many reviewers have contributed their expertise and time to the peer review,a critical process to ensure the quality of our World Series Journals.Both the editors of the journals and authors of the manuscripts submitted to the journals are grateful to the following reviewers for reviewing the articles(either published or rejected) over the past period of time.
文摘Many reviewers have contributed their expertise and time to the peer review,a critical process to ensure the quality of World Journal of Gastrointestinal Pharmacology and Therapeutics.The editors and authors of the articles submitted to the journal are grateful to the
