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-infinity)] 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-infinity) values for the equiactive metabolite 25-O-deacetyl-rifabutin, were 400 +/- 184, 361 +/- 187, and 298 +/- 102 ng.hr/ml.(ABSTRACT TRUNCATED AT 250 WORDS)
Narang
P K
PK
Department of Pharmacokinetics/Dynamics, Medical Research Center, Adria Laboratories, Columbus, OH 43216-6529.
Lewis
R C
RC
Bianchine
J R
JR
D000284:Administration, Oral; D000328:Adult; D000704:Analysis of Variance; D001682:Biological Availability; D002214:Capsules; D004041:Dietary Fats / Q000494:pharmacology; D005215:Fasting; D005502:Food; D006801:Humans; D007408:Intestinal Absorption; D016018:Least-Squares Analysis; D008297:Male; D012016:Reference Values; D017828:Rifabutin; D012294:Rifamycins / Q000008:administration & dosage / Q000493:pharmacokinetics*; D012996:Solutions
D002214:Capsules; D004041:Dietary Fats; D012294:Rifamycins; D012996:Solutions; D017828:Rifabutin