Population pharmacokinetic drug-drug interaction pooled analysis of existing data for rifabutin and HIV PIs

The Journal of Antimicrobial Chemotherapy
Stefanie HennigMats O Karlsson

Abstract

Extensive but fragmented data from existing studies were used to describe the drug-drug interaction between rifabutin and HIV PIs and predict doses achieving recommended therapeutic exposure for rifabutin in patients with HIV-associated TB, with concurrently administered PIs. Individual-level data from 13 published studies were pooled and a population analysis approach was used to develop a pharmacokinetic model for rifabutin, its main active metabolite 25-O-desacetyl rifabutin (des-rifabutin) and drug-drug interaction with PIs in healthy volunteers and patients who had HIV and TB (TB/HIV). Key parameters of rifabutin affected by drug-drug interaction in TB/HIV were clearance to routes other than des-rifabutin (reduced by 76%-100%), formation of the metabolite (increased by 224% in patients), volume of distribution (increased by 606%) and distribution to the peripheral compartment (reduced by 47%). For des-rifabutin, clearance was reduced by 35%-76% and volume of distribution increased by 67%-240% in TB/HIV. These changes resulted in overall increased exposure to rifabutin in TB/HIV patients by 210% because of the effects of PIs and 280% with ritonavir-boosted PIs. Given together with non-boosted or ritonavir-boosted PIs, rifab...Continue Reading

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Citations

Mar 28, 2017·Expert Opinion on Pharmacotherapy·Helena RabieH Simon Schaaf
Mar 24, 2018·Southern African Journal of HIV Medicine·Graeme MeintjesFrancois Venter
Dec 7, 2018·Expert Review of Anti-infective Therapy·Helen McIlleron, Maxwell T Chirehwa
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Jul 6, 2019·The Lancet. HIV·Graeme MeintjesGary Maartens
Oct 27, 2020·Southern African Journal of HIV Medicine·Jeremy NelJoana F Woods

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