title: Effect of concomitantly administered rifampin on the pharmacokinetics and safety of atazanavir administered twice daily.
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.
authors.affiliation: University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Edward P
authors.initials: EP
authors.lastname: Acosta
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Kendall
authors.forename: John G
authors.initials: JG
authors.lastname: Gerber
authors.forename: Beverly
authors.initials: B
authors.lastname: Alston-Smith
authors.forename: Susan L
authors.initials: SL
authors.lastname: Koletar
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Zolopa
authors.forename: Sangeeta
authors.initials: S
authors.lastname: Agarwala
authors.forename: Michael
authors.initials: M
authors.lastname: Child
authors.forename: Richard
authors.initials: R
authors.lastname: Bertz
authors.forename: Lara
authors.initials: L
authors.lastname: Hosey
authors.forename: David W
authors.initials: DW
authors.lastname: Haas
mesh_terms: D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D000995:Antitubercular Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D019540:Area Under Curve; D000069446:Atazanavir Sulfate; D001711:Biotransformation; D004347:Drug Interactions; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy*; D006207:Half-Life; D006801:Humans; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D011725:Pyridines / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D012293:Rifampin / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D014376:Tuberculosis / Q000150:complications / Q000188:drug therapy*
chemical_list: D019380:Anti-HIV Agents; D000995:Antitubercular Agents; D009842:Oligopeptides; D011725:Pyridines; D000069446:Atazanavir Sulfate; D012293:Rifampin