Population pharmacokinetics of rifampicin and 25-deacetyl-rifampicin in healthy Asian adults

The Journal of Antimicrobial Chemotherapy
Kok-Yong SengLawrence Soon-U Lee

Abstract

Rifampicin is a first-line anti-TB drug. The objectives of this analysis were to evaluate the population pharmacokinetics of rifampicin and its partly active metabolite, 25-deacetyl-rifampicin, with and without isoniazid, and to identify covariates that may explain variability in their disposition under steady-state conditions. Thirty-four healthy Asian subjects were randomized to receive rifampicin (600 mg) or rifampicin (600 mg)/isoniazid (300 mg) daily for 14 days. After a 14 day washout, subjects were switched over to rifampicin (600 mg)/isoniazid (300 mg) or rifampicin (600 mg) daily. Plasma concentration-time data were analysed using NONMEM to estimate population pharmacokinetic parameters and evaluate relationships between parameters and demographic factors, and metabolic enzyme, transporter and transcriptional regulator genotypes. Allometric scaling of clearance and volume of distribution terms based on body weight was applied. A one-compartment model in which absorption was described by a transit absorption model best described the rifampicin data. 25-Deacetyl-rifampicin pharmacokinetic data were best described by a two-compartment model linked to the rifampicin model. None of the investigated covariates significantly ...Continue Reading

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Citations

Aug 19, 2015·Antimicrobial Agents and Chemotherapy·Kok-Yong SengLawrence Soon-U Lee
Jan 24, 2019·Clinical Pharmacokinetics·Stijn W van BeekElin M Svensson
Apr 3, 2019·Therapeutic Drug Monitoring·Ana P Huerta-GarcíaRosa Del Carmen Milán-Segovia
Jun 17, 2016·European Journal of Clinical Pharmacology·Roger K VerbeeckTim W Rennie
Nov 5, 2016·British Journal of Clinical Pharmacology·Amélie MarsotOlivier Blin
Jan 20, 2021·British Journal of Clinical Pharmacology·Yazhou GaoJan-Willem Alffenaar
Mar 7, 2021·Clinical Pharmacokinetics·Marieke G G SturkenboomJan-Willem C Alffenaar

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