دورية أكاديمية
Population pharmacokinetics and enterohepatic recirculation of hyzetimibe and its main metabolite in Chinese healthy subjects.
| العنوان: | Population pharmacokinetics and enterohepatic recirculation of hyzetimibe and its main metabolite in Chinese healthy subjects. |
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| المؤلفون: | Chen W; Center of Clinical Pharmacology, the Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China., Ruan Z; Center of Clinical Pharmacology, the Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China., Chen J; Center of Clinical Pharmacology, the Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China., Yang D; Center of Clinical Pharmacology, the Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China., Shao R; Center of Clinical Pharmacology, the Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China., Lou H; Center of Clinical Pharmacology, the Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China., Jiang B; Center of Clinical Pharmacology, the Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China. |
| المصدر: | British journal of clinical pharmacology [Br J Clin Pharmacol] 2022 Jul; Vol. 88 (7), pp. 3153-3161. Date of Electronic Publication: 2022 Feb 07. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Wiley-Blackwell Country of Publication: England NLM ID: 7503323 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1365-2125 (Electronic) Linking ISSN: 03065251 NLM ISO Abbreviation: Br J Clin Pharmacol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Oxford : Wiley-Blackwell Original Publication: London, Macmillan Journals Ltd. |
| مواضيع طبية MeSH: | Azetines* , Models, Biological*, China ; Female ; Fluorobenzenes ; Healthy Volunteers ; Humans ; Male ; Randomized Controlled Trials as Topic |
| مستخلص: | Aims: Hyzetimibe (HS-25), a new drug approved for hypercholesterolaemia, exhibits obvious enterohepatic recirculation (EHC) after oral administration. Up to now, little is known about the kinetics of HS-25. Therefore, we performed this population pharmacokinetic (PopPK) analysis aiming to describe the PK behaviour of HS-25 and its main metabolite (M1), and to identify significant covariates contributing to the variability. Methods: The plasma concentration data used for modelling were obtained from an open-label, single-dose, randomized, 2-period crossover bioequivalence study. PopPK modelling was performed with NONMEM 7.4.1 using nonlinear mixed effect modelling approach. Goodness of fit plots, bootstrap and visual predictive check were used for model internal validation. Data from another study were used for external validation. Results: Data from 16 male and 8 female subjects were used in the PopPK analysis. HS-25 and M1 concentrations in the modelling cohort were well described by a 1-compartment model incorporating first-pass metabolism and a gallbladder compartment, accounting for the EHC process. The release kinetic of gall was mimicked by a first-order constant plus a switch on/off effect. Body weight was identified as a significant covariate effecting on the clearance and apparent distribution volume of HS-25, as well as k mg , the transfer rate from metabolite compartment to gallbladder compartment. Internal and external validation demonstrated an acceptable predictive ability of the final model. Conclusion: We present the first PopPK model describing HS-25 and M1 concentrations simultaneously, with the EHC process considered. The modelling and simulation results could provide reference for the clinical use of HS-25. (© 2021 British Pharmacological Society.) |
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| فهرسة مساهمة: | Keywords: enterohepatic recirculation; hyzetimibe; population pharmacokinetics |
| المشرفين على المادة: | 0 (1-(4-fluorophenyl)-3-(3-(4-fluorophenyl)-4-hydroxybut-2-enyl)-4-(4-hydroxyphenyl)-2-azetidinone) 0 (Azetines) 0 (Fluorobenzenes) |
| تواريخ الأحداث: | Date Created: 20211221 Date Completed: 20220615 Latest Revision: 20220626 |
| رمز التحديث: | 20231215 |
| DOI: | 10.1111/bcp.15187 |
| PMID: | 34931372 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1365-2125 |
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| DOI: | 10.1111/bcp.15187 |