Effect of concomitantly administered rifampin on the pharmacokinetics and safety of atazanavir administered twice daily.

TitleEffect of concomitantly administered rifampin on the pharmacokinetics and safety of atazanavir administered twice daily.
Publication TypeJournal Article
Year of Publication2007
AuthorsAcosta EP, Kendall MA, Gerber JG, Alston-Smith B, Koletar SL, Zolopa AR, Agarwala S, Child M, Bertz R, Hosey L, Haas DW
JournalAntimicrob Agents Chemother
Volume51
Issue9
Pagination3104-10
Date Published2007 Sep
ISSN0066-4804
KeywordsAdolescent, Adult, Anti-HIV Agents, Antitubercular Agents, Area Under Curve, Atazanavir Sulfate, Biotransformation, Drug Interactions, Female, Half-Life, HIV Infections, Humans, Male, Middle Aged, Oligopeptides, Pyridines, Rifampin, Tuberculosis
Abstract

The potent induction of hepatic cytochrome P450 3A isoforms by rifampin complicates therapy for coinfection with human immunodeficiency virus (HIV) and Mycobacterium tuberculosis. We performed an open-label, single-arm study to assess the safety and pharmacokinetic interactions of the HIV protease inhibitor atazanavir coadministered with rifampin. Ten healthy HIV-negative subjects completed pharmacokinetic sampling at steady state while receiving 300 mg atazanavir every 12 h without rifampin (period 1), 300 mg atazanavir every 12 h with 600 mg rifampin every 24 h (period 2), and 400 mg atazanavir every 12 h with 600 mg rifampin every 24 h (period 3). During period 1, the mean concentration of drug in serum at 12 h (C(12 h)) was 811 ng/ml (range, 363 to 2,484 ng/ml) for atazanavir, similar to historic seronegative data for once-daily treatment with 300 mg atazanavir boosted with 100 mg ritonavir. During periods 2 and 3, the mean C(12 h) values for atazanavir were 44 ng/ml (range, <25 to 187 ng/ml) and 113 ng/ml (range, 39 to 260 ng/ml), respectively, well below historic seronegative data for once-daily treatment with 400 mg atazanavir without ritonavir. Although safe and generally well tolerated, 300 mg or 400 mg atazanavir administered every 12 h did not maintain adequate plasma exposure when coadministered with rifampin.

DOI10.1128/AAC.00341-07
Alternate JournalAntimicrob. Agents Chemother.
PubMed ID17576825
PubMed Central IDPMC2043180
Grant ListAI068636 / AI / NIAID NIH HHS / United States
AI069439 / AI / NIAID NIH HHS / United States
AI069474 / AI / NIAID NIH HHS / United States
AI32775 / AI / NIAID NIH HHS / United States
AI38855 / AI / NIAID NIH HHS / United States
AI38858 / AI / NIAID NIH HHS / United States
AI68636 / AI / NIAID NIH HHS / United States
RR000034 / RR / NCRR NIH HHS / United States
RR00095 / RR / NCRR NIH HHS / United States