• CYP3A;
  • HIV;
  • interaction;
  • pharmacokinetics;
  • rifabutin;
  • saquinavir

Aims  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 Cmax(0,8 h) of 47% (95% CI 30, 60%) and 39% (95% CI 11, 59%), respectively. Rifabutin AUC(0,24 h) and Cmax(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.