Effect of efavirenz-based antiretroviral therapy and high-dose rifampicin on the pharmacokinetics of isoniazid and acetyl-isoniazid.

The Journal of Antimicrobial Chemotherapy
Maxwell ChirehwaRAFA team

Abstract

To describe the pharmacokinetics of isoniazid and acetyl-isoniazid in TB/HIV-coinfected patients, and assess the effects of efavirenz co-administration and a 50% increase in the dose of rifampicin on the pharmacokinetic parameters of isoniazid and acetyl-isoniazid. TB/HIV-coinfected patients participating in the three-treatment-arm RAFA randomized controlled trial conducted in West Africa were recruited into the pharmacokinetics sub-study. Five serial blood samples were collected on a single visit between 4 and 8 weeks after initiation of antituberculosis treatment. Concentration-time data for isoniazid and acetyl-isoniazid were analysed using non-linear mixed-effects models. Isoniazid concentrations from 150 patients were available for analysis, and 79 of these (53%) also had concentrations of acetyl-isoniazid. Isoniazid pharmacokinetics was best described with a two-compartment disposition model with lagged first-order absorption and elimination using a semi-mechanistic model describing hepatic extraction. The model identified two elimination pathways, separating formation of acetyl-isoniazid from other routes of metabolism. The predicted AUC0-24 is reduced by 29% in patients who are fast acetylators of isoniazid and receivin...Continue Reading

References

Apr 1, 1976·Journal of Pharmacokinetics and Biopharmaceutics·G A Ellard, P T Gammon
Jan 1, 1976·Nephron·D W Cockcroft, M H Gault
Aug 8, 1991·Biochemical Pharmacology·D Hickman, E Sim
May 1, 1997·American Journal of Respiratory and Critical Care Medicine·D P ParkinP P van Jaarsveld
Oct 6, 1997·American Journal of Respiratory and Critical Care Medicine·P R DonaldD A Mitchison
Mar 21, 1998·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·J O ClemmesenP Ott
Jan 8, 1999·Drugs·J C Adkins, S Noble
Nov 27, 1999·The Journal of Biological Chemistry·M A LeffD W Hein
Jan 5, 2002·Journal of Pharmacokinetics and Pharmacodynamics·S L Beal
Jul 17, 2004·British Journal of Clinical Pharmacology·Bruce Green, Stephen B Duffull
Nov 17, 2004·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·P R DonaldJ S Maritz
Sep 27, 2005·Clinica Chimica Acta; International Journal of Clinical Chemistry·Bing ChenXiao-Mei Cao
Jul 27, 2007·Journal of Pharmacokinetics and Pharmacodynamics·Radojka M SavicMats O Karlsson
Oct 5, 2007·Annual Review of Pharmacology and Toxicology·B J Anderson, N H G Holford
Feb 29, 2008·Pharmacogenomics·Puspita Das RoyBidyut Roy
Oct 22, 2008·International Review of Neurobiology·Gail D Anderson
Feb 16, 2011·British Journal of Clinical Pharmacology·Justin J WilkinsUlrika S H Simonsson
Apr 3, 2012·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Jotam G PasipanodyaTawanda Gumbo
Jul 10, 2013·CPT: Pharmacometrics & Systems Pharmacology·R J KeizerA Hooker
Mar 26, 2014·Antimicrobial Agents and Chemotherapy·N B BhattUNKNOWN ANRS 12146-CARINEMO Study Group
May 23, 2014·Drugs·Abdullah Alsultan, Charles A Peloquin
Aug 19, 2015·Antimicrobial Agents and Chemotherapy·Kok-Yong SengLawrence Soon-U Lee
Oct 7, 2016·Acta Pharmaceutica Sinica. B·Pengcheng WangXiaochao Ma
Nov 3, 2016·Expert Review of Clinical Pharmacology·Bella Devaleenal DanielSoumya Swaminathan
Jan 20, 2017·The Lancet Infectious Diseases·Martin J BoereeUNKNOWN PanACEA consortium

❮ Previous
Next ❯

Citations

Dec 7, 2018·Expert Review of Anti-infective Therapy·Helen McIlleron, Maxwell T Chirehwa
Oct 28, 2020·Antimicrobial Agents and Chemotherapy·K B ArunR Ajay Kumar

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antitubercular Agents (ASM)

Antitubercular agents are pharmacologic agents for treatment of tuberculosis. Discover the latest research on antitubercular agents here.

Antitubercular Agents

Antitubercular agents are pharmacologic agents for treatment of tuberculosis. Discover the latest research on antitubercular agents here.