Chandler M H, Scott S R, Blouin R A
Drug Product Evaluation Unit, University of Kentucky College of Pharmacy, Lexington 40536-0082.
Clin Pharmacol Ther. 1988 Apr;43(4):436-41. doi: 10.1038/clpt.1988.55.
This clinical investigation was designed to study the influence of age on stereoselective drug disposition using hexobarbital as a model marker. The disposition of hexobarbital enantiomers was investigated in 10 young and 10 elderly, healthy male volunteers. Mean oral clearance (+/- SD) of d-hexobarbital (1.9 +/- 0.5 vs. 1.7 +/- 0.3 ml/min/kg; P greater than 0.05) did not differ significantly between the young and elderly subjects, respectively. However, despite wide intersubject variability, l-hexobarbital mean oral clearance (+/- SD) was approximately twofold greater in the young than in the elderly subjects (16.9 +/- 11.9 vs. 8.2 +/- 3.2 ml/min/kg; P less than 0.05). This resulted in a significantly greater enantiomeric oral clearance ratio in the young when compared with the elderly subjects (8.3 +/- 3.4 vs. 4.7 +/- 1.4; P less than 0.01). No significant difference (P greater than 0.05) in pharmacologic response after hexobarbital administration was found between the two groups. Demonstration of an age-related preferential decline in metabolism of one enantiomer over another has not been reported previously for any racemic drug in animals or humans.
本临床研究旨在以己巴比妥作为模型标记物，研究年龄对立体选择性药物处置的影响。在10名年轻和10名老年健康男性志愿者中研究了己巴比妥对映体的处置情况。年轻和老年受试者中，右旋己巴比妥的平均口服清除率（±标准差）分别为（1.9±0.5对1.7±0.3 ml/min/kg；P>0.05），无显著差异。然而，尽管个体间差异较大，但左旋己巴比妥的平均口服清除率（±标准差）在年轻人中约为老年人的两倍（16.9±11.9对8.2±3.2 ml/min/kg；P<0.05）。这导致年轻人的对映体口服清除率比值显著高于老年人（8.3±3.4对4.7±1.4；P<0.01）。两组在给予己巴比妥后的药理反应上无显著差异（P>0.05）。此前尚未有报道称，对于任何动物或人类的外消旋药物，一种对映体的代谢会随年龄出现优先下降。
