title: Evaluation of the effect of fluconazole on the pharmacokinetics of ritonavir.
abstract: 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 AUC0-24 (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 beta were not statistically significantly different. Although some ritonavir parameters were affected by fluconazole, mean increases in C(max) and AUC were < or = 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.
authors.affiliation: Pharmaceutical Products Division, Abbott Laboratories, Abbott Park, IL 60064, USA.
authors.forename: A
authors.initials: A
authors.lastname: Cato
authors.forename: G
authors.initials: G
authors.lastname: Cao
authors.forename: A
authors.initials: A
authors.lastname: Hsu
authors.forename: J
authors.initials: J
authors.lastname: Cavanaugh
authors.forename: J
authors.initials: J
authors.lastname: Leonard
authors.forename: R
authors.initials: R
authors.lastname: Granneman
mesh_terms: D000328:Adult; D000935:Antifungal Agents / Q000494:pharmacology*; D019540:Area Under Curve; D018592:Cross-Over Studies; D004347:Drug Interactions; D005260:Female; D015725:Fluconazole / Q000494:pharmacology*; D017320:HIV Protease Inhibitors / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D019438:Ritonavir / Q000493:pharmacokinetics*
chemical_list: D000935:Antifungal Agents; D017320:HIV Protease Inhibitors; D015725:Fluconazole; D019438:Ritonavir