Narang P K, Lewis R C, Bianchine J R
Department of Pharmacokinetics/Dynamics, Medical Research Center, Adria Laboratories, Columbus, OH 43216-6529.
Clin Pharmacol Ther. 1992 Oct;52(4):335-41. doi: 10.1038/clpt.1992.152.
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)
在一项针对12名健康男性志愿者的利福布汀随机三交叉试验中，评估了胶囊剂型（150毫克）的相对生物利用度以及高脂食物的影响。每位受试者接受单次150毫克剂量，分别为溶液（治疗A，空腹）、进食时服用胶囊（治疗B）和空腹服用胶囊（治疗C），洗脱期为2周。分别在168小时和48小时采集系列血浆和尿液样本，通过经过验证的高效液相色谱法对利福布汀及其活性代谢物25 - O - 去乙酰基利福布汀进行定量。利福布汀在血浆中的平均±标准差最大浓度分别为238±65、156±52和188±50纳克/毫升，达到峰值浓度的时间分别为2.5±0.4、5.4±1.6和3.0±1.1小时，血浆浓度 - 时间曲线从零至无穷大的面积[AUC(0 - ∞)]在空腹状态下溶液剂型和胶囊剂型分别为2989±726、2640±891和2516±601纳克·小时/毫升。治疗A、B、C中以未改变的利福布汀形式经尿液排泄的剂量百分比分别为11.0%±2.4%、11.4%±4.9%和9.1%±2.1%。等活性代谢物25 - O - 去乙酰基利福布汀相应的AUC(0 - ∞)值分别为400±184、361±187和298±102纳克·小时/毫升。（摘要截短至250字）
