Christensen Michael L, Meibohm Bernd, Capparelli Edmund V, Velasquez-Mieyer Pedro, Burghen George A, Tamborlane William V
University of Tennessee, 50 North Dunlap, Room 306, Memphis, TN 38103, USA.
J Clin Pharmacol. 2005 Oct;45(10):1137-44. doi: 10.1177/0091270005279578.
This study assessed the single- and multiple-dose pharmacokinetics of 3 doses (15 mg, 30 mg, and 45 mg) of pioglitazone in 36 adolescents with type 2 diabetes. Blood samples were obtained over a 48-hour interval after the first dose (day 1) and over a 72-hour interval after the last dose (day 15) of pioglitazone and were assayed for pioglitazone and active metabolites (M-III and M-IV). Pioglitazone systemic exposure increased dose dependently but was less than dose proportional during multiple dosing. The median peak pioglitazone concentration occurred at 2 hours. The mean half-life was 8 to 9 hours for pioglitazone and 24 to 32 hours for M-III and M-IV, with similar values at each dose level. During multiple dosing, accumulation for pioglitazone was negligible, but it reached 2.5- to 3.0-fold for M-III and M-IV. The sustained total serum concentration of active compounds during multiple dosing provides the basis for once-daily dose administration of pioglitazone in adolescents.
本研究评估了3种剂量（15毫克、30毫克和45毫克）的吡格列酮在36例2型糖尿病青少年中的单剂量和多剂量药代动力学。在首次服用吡格列酮后（第1天）的48小时间隔内以及最后一次服用吡格列酮后（第15天）的72小时间隔内采集血样，并对血样进行吡格列酮及其活性代谢物（M-III和M-IV）的检测。吡格列酮的全身暴露量呈剂量依赖性增加，但在多次给药期间小于剂量比例增加。吡格列酮的中位峰浓度出现在2小时。吡格列酮的平均半衰期为8至9小时，M-III和M-IV的平均半衰期为24至32小时，各剂量水平下的值相似。在多次给药期间，吡格列酮的蓄积可忽略不计，但M-III和M-IV的蓄积达到2.5至3.0倍。多次给药期间活性化合物的持续总血清浓度为青少年吡格列酮每日一次给药提供了依据。
