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Safety, tolerability, and pharmacokinetic interactions between single-dose TMC207 and steady-state efavirenz in healthy volunteers: AIDS Clinical Trials Group (ACTG) Study.
Journal of Acquired Immune Deficiency Syndromes
Background: Drug-drug interactions complicate management of coinfection with HIV-1 and Mycobacterium tuberculosis. Bedaquiline (formerly TMC207), an investigational agent for the treatment of tuberculosis, is metabolized by cytochrome P450 (CYP) 3A which may be induced by the antiretroviral drug efavirenz.
Methods: This was a phase 1 pharmacokinetic drug interaction trial. Each healthy volunteer received two 400 mg doses of bedaquiline, the first alone and the second with concomitant steady-state efavirenz. Plasma pharmacokinetic sampling for bedaquiline and its N-monodesmethyl metabolite was performed over 14 days after each bedaquiline dose. Steady-state efavirenz pharmacokinetics were also determined. Efavirenz metabolizer status was based on CYP2B6 composite 516/983 genotype.
Dooley KE, Park J-G, Swindells S, Allen R, Haas DW, Aweeka F, Gupta A, Lizak P, Qasba S, Cramer Y, van Heeswijk R, Flexner C. Safety, tolerability, and pharmacokinetic interactions between single-dose TMC207 and steady-state efavirenz in healthy volunteers: AIDS Clinical Trials Group (ACTG) Study. J Acquir Immune Defic Syndr. 2012 Apr; 15;59(5):455-62. PMCID:PMC3302922