Rifabutin absorption in humans: Relative bioavailability and food effect

The relative bioavailability of the capsule dose form (150 mg) and the effect of high-fat food were assessed in a randomized, three-way crossover trial of rifabutin in 12 healthy male volunteers. Each subject received a single 150 mg dose as a solution (treatment A, fasted) or a capsule with food (treatment B) and without food (treatment C), with a 2-week washout period. Serial plasma and urine samples were obtained for 168 and 48 hours, respectively, and rifabutin and its active metabolite, 25-O-deacetyl-rifabutin, quantitated by a validated HPLC procedure. The mean ± SD maximum concentration for rifabutin in plasma was 238 ± 65, 156 ± 52, and 188 ± 50 ng/ml, time to reach peak concentration was 2.5 ± 0.4, 5.4 ± 1.6, and 3.0 ± 1.1 hours, and the area under the plasma concentration-time curve from zero to infinity [AUC(0-∞)] was 2989 ± 726, 2640 ± 891, and 2516 ± 601 ng • hr/ml for the solution and the capsule during the fed and fasted states, respectively. Percentage of dose excreted in the urine as unchanged rifabutin was 11.0% ± 2.4%, 11.4% ± 4.9%, and 9.1% ± 2.1% for treatments A, B, and C, respectively. The corresponding AUC(0-∞) values for the equiactive metabolite 25-O-deacetyl-rifabutin, were 400 ± 184, 361 ± 187, and 298 ± 102 ng • hr/ml. ANOVA showed a significant decrease (p = 0.027) in the maximum concentration for rifabutin after administration of the capsule compared with the solution during the fasted state and a significant increase (p = 0.0001) in the time to reach maximum concentration of rifabutin when the capsule was given with food (compared with capsule given after subjects had fasted). Although the rate of rifabutin absorption appears to be slower in the presence of high-fat food, the extent of absorption from the capsule form is not altered. Mean relative bioavailability for the capsule (fasted) was 84.8% ± 18.5%, whereas the mean relative bio-availability (fed/fasted) was 106.0% ± 24.1%. These data suggest that the tissue exposure to this antimy-cobacterial agent is not expected to be altered by food. Rifabutin can therefore be administered with or without food for prophylaxis of Mycobacterium avium complex. Clinical Pharmacology and Therapeutics (1992) 52, 335–341; doi:10.1038/clpt.1992.152