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基于性别差异的成年男性和女性美托洛尔剂量等效性:药代动力学建模与模拟

Metoprolol Dose Equivalence in Adult Men and Women Based on Gender Differences: Pharmacokinetic Modeling and Simulations.

作者信息

Eugene Andy R

机构信息

Division of Clinical Pharmacology, Department of Molecular Pharmacology and Experimental Therapeutics, Gonda 19, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA;

出版信息

Med Sci (Basel). 2016;4(4). doi: 10.3390/medsci4040018. Epub 2016 Nov 15.

Abstract

Recent meta-analyses and publications over the past 15 years have provided evidence showing there are considerable gender differences in the pharmacokinetics of metoprolol. Throughout this time, there have not been any research articles proposing a gender stratified dose-adjustment resulting in an equivalent total drug exposure. Metoprolol pharmacokinetic data was obtained from a previous publication. Data was modeled using nonlinear mixed effect modeling using the MONOLIX software package to quantify metoprolol concentration-time data. Gender-stratified dosing simulations were conducted to identify equivalent total drug exposure based on a 100 mg dose in adults. Based on the pharmacokinetic modeling and simulations, a 50 mg dose in adult women provides an approximately similar metoprolol drug exposure to a 100 mg dose in adult men.

摘要

最近的荟萃分析以及过去15年发表的文献表明,美托洛尔的药代动力学存在显著的性别差异。在此期间,没有任何研究文章提出进行性别分层剂量调整以实现等效的总药物暴露。美托洛尔的药代动力学数据来自之前的一篇出版物。使用MONOLIX软件包通过非线性混合效应模型对数据进行建模,以量化美托洛尔的浓度-时间数据。进行了性别分层给药模拟,以确定基于成人100毫克剂量的等效总药物暴露。基于药代动力学建模和模拟,成年女性50毫克的剂量与成年男性100毫克的剂量产生的美托洛尔药物暴露大致相似。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d671/5635791/476117e84f75/medsci-04-00018-g001.jpg

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