The effect of fluconazole on ritonavir and saquinavir pharmacokinetics in HIV-1-infected individuals

Aims To study the effect of fluconazole on the steady-state pharmacokinetic s of the protease inhibitors ritonavir and saquinavir in HIV-1-infected pat ients. Methods Five subjects treated with saquinavir and three with ritonavir rece ived the protease inhibitor alone (saquinavir 1200 mg three times daily, ri tonavir 600 mg twice daily) on day 1, and the same protease inhibitor in co mbination with fluconazole (400 mg on day 2 and 200 mg on days 3 to 8). Pha rmacokinetic parameters were determined on days 1 and 8. Results In the saquinavir group, the median increase in the area under the plasma concentration vs time curve was 50% from 1800 mug 1(-1) h to 2700 mu g l(-1) h (P = 0.04, median increase: 900 mug 1(-1) h; 2.5 and 97.5 percent ile: 500-1300), and 56% for the peak concentration in plasma (from 550 to 8 70 mug 1(-1), P=0.04; median increase: 320 mug 1(-1) h, 2.5 and 97.5 percen tile: 60-450 mug 1(-1)). In the ritonavir group, there were no detectable c hanges in the pharmacokinetic parameters on addition of fluconazole. Conclusions Because of the favourable safety profile of saquinavir, dose ad justments are probably not necessary with concomitant use of fluconazole, a s is the case for ritonavir.