دورية أكاديمية
Physiologically based pharmacokinetic modeling to characterize enterohepatic recirculation and predict food effect on the pharmacokinetics of hyzetimibe.
| العنوان: | Physiologically based pharmacokinetic modeling to characterize enterohepatic recirculation and predict food effect on the pharmacokinetics of hyzetimibe. |
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| المؤلفون: | Chen W; Center of Clinical Pharmacology, the Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China., Ruan Z; Center of Clinical Pharmacology, the Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China., Lou H; Center of Clinical Pharmacology, the Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China., Yang D; Center of Clinical Pharmacology, the Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China., Chen J; Center of Clinical Pharmacology, the Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China., Shao R; Center of Clinical Pharmacology, the Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China., Jiang B; Center of Clinical Pharmacology, the Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China. Electronic address: jiangbo@zju.edu.cn. |
| المصدر: | European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences [Eur J Pharm Sci] 2023 Nov 01; Vol. 190, pp. 106576. Date of Electronic Publication: 2023 Sep 06. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Science B.V Country of Publication: Netherlands NLM ID: 9317982 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-0720 (Electronic) Linking ISSN: 09280987 NLM ISO Abbreviation: Eur J Pharm Sci Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Amsterdam : Elsevier Science B.V Original Publication: Amsterdam ; New York : Elsevier, c1993- |
| مواضيع طبية MeSH: | Azetines* , Anticholesteremic Agents*, Fluorobenzenes ; Fasting/metabolism ; Therapeutic Equivalency ; Cross-Over Studies ; Area Under Curve ; Healthy Volunteers |
| مستخلص: | Background and Objective: Hyzetimibe is a cholesterol absorption inhibitor indicated for the treatment of hypercholesterolemia. This study aims to describe the multiple-peak pharmacokinetics (PK) of hyzetimibe and its active metabolite M1 through physiologically-based pharmacokinetic (PBPK) modeling, and to compare the model predictions of a virtual food effect study with the results of a clinical food effect study. Methods: The plasma concentration data used for PBPK modeling were obtained from a single-dose, two-period crossover bioequivalence study in the fasted state. Advanced Compartmental Absorption and Transit model was used for absorption. Enterohepatic recirculation process was modeled by changing the gut physiological state from fasted to fed at meal time. Based on the established PBPK models, a virtual food effect study was simulated. A clinical food effect study was used for model external validation. Results: PK profiles of hyzetimibe and M1 under fasting condition could be well described by the PBPK model, and the errors of C Conclusions: The established PBPK model could describe the concentration-time profiles of hyzetimibe and M1 well with good prediction performance. A fully mechanistic model of enterohepatic recirculation warrants further investigation. Competing Interests: Declaration of Competing Interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2023 The Second Affiliated Hospital of Zhejiang University School of Medicine. Published by Elsevier B.V. All rights reserved.) |
| فهرسة مساهمة: | Keywords: Enterohepatic recirculation; Food effect; Hyzetimibe; Pharmacokinetics; Physiologically-based pharmacokinetic modeling |
| المشرفين على المادة: | 0 (1-(4-fluorophenyl)-3-(3-(4-fluorophenyl)-4-hydroxybut-2-enyl)-4-(4-hydroxyphenyl)-2-azetidinone) 0 (Azetines) 0 (Fluorobenzenes) 0 (Anticholesteremic Agents) |
| تواريخ الأحداث: | Date Created: 20230907 Date Completed: 20231002 Latest Revision: 20231002 |
| رمز التحديث: | 20231002 |
| DOI: | 10.1016/j.ejps.2023.106576 |
| PMID: | 37678518 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1879-0720 |
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| DOI: | 10.1016/j.ejps.2023.106576 |