TY - JOUR T1 - Evaluation of the Effect of Fluconazole on the Pharmacokinetics of Ritonavir JF - Drug Metabolism and Disposition JO - Drug Metab Dispos SP - 1104 LP - 1106 VL - 25 IS - 9 AU - Allen Cato III AU - Guoliang Cao AU - Ann Hsu AU - John Cavanaugh AU - John Leonard AU - Richard Granneman Y1 - 1997/09/01 UR - http://dmd.aspetjournals.org/content/25/9/1104.abstract N2 - The effects of fluconazole on the pharmacokinetics of the HIV protease inhibitor ritonavir were investigated after multiple dosing in an open-label study. In this randomized, two-period crossover study, eight healthy subjects received ritonavir alone (200 mg every 6 hr for 4 days) and ritonavir with fluconazole (400 mg on day 1, 200 mg every day on days 2–5) with a 2-week washout period. Ritonavir plasma concentrations were measured during the final four ritonavir dosing intervals (24 hr) and a 12-hr washout period. There were statistically significant increases in ritonavir Cmax and AUC0–24 (p < 0.02), with concurrent administration of fluconazole compared with administration of ritonavir alone. The difference between regimens inCmin was marginally statistically significant (p = 0.089), and tmaxand β were not statistically significantly different. Although some ritonavir parameters were affected by fluconazole, mean increases inCmax and AUC were ≤15% for the 24-hr period, and only 7–19% for individual dose intervals. Thus, the pharmacokinetics of ritonavir may be influenced only to a small extent when administered with fluconazole. These changes are probably of limited clinical significance and do not necessitate dosage adjustment of ritonavir when fluconazole is added to the regimen. The American Society for Pharmacology and Experimental Therapeutics ER -