Simulation of the Pharmacokinetics of Oseltamivir and Its Active Metabolite in Normal Populations and Patients with Hepatic Cirrhosis Using Physiologically Based Pharmacokinetic Modeling

AAPS PharmSciTech
Yong ChenCuihong Lin

Abstract

Oseltamivir is a neuraminidase inhibitor widely used to treat and prevent influenza A and B infections, although its safety and pharmacokinetics have not been evaluated in patients with severe hepatic impairment. A physiologically based pharmacokinetic (PBPK) model of the prodrug oseltamivir and its active metabolite, oseltamivir carboxylate (OC), was established and validated to simulate their disposition in adults and predict the exposure in patients with Child-Pugh C cirrhosis (CP-C). The simulated results from PBPK modeling and the observed data after oral administration of various oseltamivir regimens were consistent according to the fold error values of less than 2. Furthermore, the clinical observations published in the literature were comparable with our pharmacokinetic predictions. In patients with CP-C, the oseltamivir Cmax was approximately 2-fold increased, and its AUC was approximately 6-fold higher compared with those in normal subjects. In contrast, the AUC of OC in CP-C patients did not differ significantly from that in normal subjects, whereas its Cmax was reduced by approximately 30% in the patients. Examination of drug exposure in different health conditions indicated that the oseltamivir exposure was signifi...Continue Reading

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Citations

Jul 31, 2021·International Journal of Nanomedicine·Ran ChenJingqing Zhang

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Software Mentioned

Gastroplus
Graphpad
GetData Graph Digitizer
SimPeff
Population Simulator
GraphPad Prism

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