Age-associated stereoselective alterations in hexobarbital metabolism

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Abstract
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 > 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 younger than in the elderly subjects (16.9 .+-. 11.9 vs. 8.2 .+-. 3.2 ml/min/kg; P < 0.05). This result 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 < 0.01). No significant difference (P > 0.05) in pharmacologic response after hexobarbital administration wasfound 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.