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 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.
Footnotes
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Send reprint requests to: Dr. Allen Cato III, Pharmacokineticist, Pharmaceutical Products Division, D-4PK, AP13A, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064.
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Received January 9, 1997; accepted May 27, 1997.
- Abbreviations used are::
- HIV
- human immunodeficiency virus
- AIDS
- acquired immune deficiency syndrome
- CYP
- cytochrome P450
- Cmax
- maximum concentration
- Cmin
- minimum concentration
- tmax
- time to maximum concentration
- AUC
- area under the concentration-time curve for each interval
- AUC0–24
- area under the concentration-time curve for the entire 24-hr interval
- The American Society for Pharmacology and Experimental Therapeutics
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