0090-9556/97/2509-1104-1106$02.00/0
DRUG METABOLISM AND DISPOSITION
Copyright © 1997 by The American Society for Pharmacology and Experimental Therapeutics
Vol. 25, No. 9

SHORT COMMUNICATION
Evaluation of the Effect of Fluconazole on the Pharmacokinetics of Ritonavir

Allen Cato, III, Guoliang Cao, Ann Hsu, John Cavanaugh, John Leonard, and Richard Granneman

Pharmaceutical Products Division, Abbott Laboratories

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 C_max and AUC_0-24 (p < 0.02), with concurrent administration of fluconazole compared with administration of ritonavir alone. The difference between regimens in C_min was marginally statistically significant (p = 0.089), and t_max and  were not statistically significantly different. Although some ritonavir parameters were affected by fluconazole, mean increases in C_max 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.