Significant in vitro and in vivo evidence supports the potential use of sertraline as an anticancer and antimicrobial agent. Yet, it is unknown whether effective sertraline concentrations are clinically achieved at therapeutic doses. The study objectives were to develop a physiologically‐based pharmacokinetic (PBPK) model of sertraline and estimate the probability of achieving effective concentrations in various human tissues. A generic PBPK model consisting of perfusion‐limited compartments representing the body organs linked together by blood flows and incorporated with clearance, tissue distribution, and absorption models was implemented in R using the mrgsolve package. Sertraline clearance and volume of distribution were first optimized from i.v. plasma concentration data then absorption and bioavailability were optimized from oral data. Predicted unbound sertraline concentrations at steady‐state in human tissues did not reach concentrations determined in vitro , indicating therapeutic doses of sertraline are unlikely to produce concentrations required for anticancer and antimicrobial activities in humans.

中文翻译：

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舍曲林在人体中的基于生理的药代动力学模型，可预测目标组织浓度的临床相关性。

显著体外和体内证据支持舍曲林可能用作抗癌和抗菌剂。然而，尚不清楚在治疗剂量下临床上是否能达到有效的舍曲林浓度。研究目的是建立舍曲林的基于生理的药代动力学（PBPK）模型，并估计在各种人体组织中达到有效浓度的可能性。使用mrgsolve软件包在R中实现了一个通用的PBPK模型，该模型由代表血流相连的身体器官的有限灌注区室组成，并与清除，组织分布和吸收模型结合在一起。首先从静脉血浆浓度数据优化舍曲林清除率和分布体积，然后从口服数据优化吸收和生物利用度。在体外，表明舍曲林的治疗剂量不太可能产生人体抗癌和抗菌活性所需的浓度。