Interaction between saquinavir soft-gel and rifabutin in patients infected with HIV.
OBJECTIVE
To evaluate the potential pharmacokinetic interaction between the HIV protease inhibitor saquinavir and rifabutin.


METHODS
Fourteen HIV-infected patients provided full steady-state pharmacokinetic profiles following administration of rifabutin alone (300 mg once daily) or saquinavir soft-gel formulation (1200 mg three times daily) plus rifabutin (300 mg once daily) in this open label, partially randomized study.


RESULTS
Coadministration of saquinavir and rifabutin resulted in a reduction in saquinavir AUC(0,8 h) and C(max)(0,8 h) of 47% (95% CI 30, 60%) and 39% (95% CI 11, 59%), respectively. Rifabutin AUC(0,24 h) and C(max)(0,24 h) was increased by an average of 44% (95% CI 17, 78%) and 45% (95% CI 14, 85%), respectively. Saquinavir in combination with rifabutin was well tolerated. Gastrointestinal intolerance and asymptomatic increases in liver enzymes were the only adverse events of note.


CONCLUSIONS
Administration of rifabutin with saquinavir may decrease the efficacy of this HIV protease inhibitor.
Moyle
G J
GJ
Kobler Clinic, Chelsea and Westminster Hospital, 369 Fulham Rd, London SW10 9NH, UK. gm@moyleg.demon.co.uk
Buss
N E
NE
Goggin
T
T
Snell
P
P
Higgs
C
C
Hawkins
D A
DA
D000328:Adult; D001682:Biological Availability; D018592:Cross-Over Studies; D004338:Drug Combinations; D004347:Drug Interactions; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D017828:Rifabutin / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019258:Saquinavir / Q000493:pharmacokinetics* / Q000627:therapeutic use
D004338:Drug Combinations; D017320:HIV Protease Inhibitors; D017828:Rifabutin; D019258:Saquinavir