Eugene Andy R
Division of Clinical Pharmacology, Department of Molecular Pharmacology and Experimental Therapeutics, Gonda 19, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA; Joyner Lab: Integrative Human Physiology and Pharmacology Lab, Department of Anesthesiology, Rochester, MN, USA.
Int J Clin Pharmacol Toxicol. 2016 May;5(3):209-215. Epub 2016 May 19.
This article seeks to clarify if gender-based differences occur in the pharmacokinetics of metoprolol in the elderly patients. There are a series of physiologic changes that occur in the elderly ranging from decreased hepatic blood flow to increased adiposity causing higher plasma concentrations at therapeutic doses as compared to the healthy young population.
Population pharmacokinetic modeling were performed using MONOLIX and Monte-Carlo simulations were conducted using MATLAB. The data was based from a previously published dataset where elderly patients, having multiple comorbidities, were administered a 50mg dose of metoprolol.
Metoprolol was modeled using a one-compartment model and resulted in the following population pharmacokinetic parameters: volume of distribution, V=38L (CV=155%), clearance rates, CL-Men=105L/hour and CL-Women=59.1L/hour (38%), time lag, Tlag=0.469 hour (CV=17%), and the absorption rate constant, Ka=0.235 hr (CV=23%).
Gender stratified doses resulting in an equivalent systemic metoprolol exposure in geriatric patients have been identified. Metoprolol doses resulting a similar AUC in a healthy young male administered 50mg tablet were 15mg for geriatric women and 25mg for geriatric men. Further, Metoprolol doses of 25mg for geriatric women and 50mg for geriatric men resulted in an equivalent AUC to a healthy young males dosed with a 100mg tablet. A 15mg Metoprolol tablet may need to be compounded to account for the gender differences in Metoprolol pharmacokinetics.
本文旨在阐明老年患者中，美托洛尔的药代动力学是否存在基于性别的差异。老年人会出现一系列生理变化，从肝血流量减少到肥胖增加，这导致与健康年轻人群相比，治疗剂量下的血浆浓度更高。
使用MONOLIX进行群体药代动力学建模，并使用MATLAB进行蒙特卡洛模拟。数据基于先前发表的数据集，其中患有多种合并症的老年患者接受了50mg剂量的美托洛尔。
美托洛尔采用单室模型进行建模，得到以下群体药代动力学参数：分布容积V = 38L（变异系数CV = 155%），清除率CL-Men = 105L/小时，CL-Women = 59.1L/小时（38%），时滞Tlag = 0.469小时（CV = 17%），吸收速率常数Ka = 0.235小时（CV = 23%）。
已确定在老年患者中，能产生等效全身美托洛尔暴露量的按性别分层的剂量。在健康年轻男性服用50mg片剂时，能产生相似曲线下面积（AUC）的美托洛尔剂量，老年女性为15mg，老年男性为25mg。此外，老年女性服用25mg、老年男性服用50mg的美托洛尔剂量，与健康年轻男性服用100mg片剂时的AUC相当。可能需要配制15mg的美托洛尔片剂，以考虑美托洛尔药代动力学中的性别差异。
