Effect of concomitantly administered rifampin on the pharmacokinetics and safety of atazanavir administered twice daily.
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.
Acosta
Edward P
EP
University of Alabama at Birmingham, Birmingham, Alabama, USA.
Kendall
Michelle A
MA
Gerber
John G
JG
Alston-Smith
Beverly
B
Koletar
Susan L
SL
Zolopa
Andrew R
AR
Agarwala
Sangeeta
S
Child
Michael
M
Bertz
Richard
R
Hosey
Lara
L
Haas
David W
DW
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*
D019380:Anti-HIV Agents; D000995:Antitubercular Agents; D009842:Oligopeptides; D011725:Pyridines; D000069446:Atazanavir Sulfate; D012293:Rifampin