Age-associated stereoselective alterations in hexobarbital metabolism.
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.
Chandler
M H
MH
Drug Product Evaluation Unit, University of Kentucky College of Pharmacy, Lexington 40536-0082.
Scott
S R
SR
Blouin
R A
RA
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000375:Aging / Q000378:metabolism*; D006591:Hexobarbital / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D011597:Psychomotor Performance / Q000187:drug effects; D013237:Stereoisomerism
D006591:Hexobarbital