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Age‐associated stereoselective alterations in hexobarbital metabolism
Author(s) -
Chandler Mary H H,
Scott Samuel R,
Blouin Robert A
Publication year - 1988
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1988.55
Subject(s) - hexobarbital , enantiomer , stereoselectivity , pharmacokinetics , disposition , pharmacology , metabolism , clinical pharmacology , oral administration , drug metabolism , chemistry , drug administration , drug , medicine , endocrinology , psychology , in vitro , biochemistry , stereochemistry , microsome , social psychology , catalysis
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 young than in the elderly subjects (16.9 ±11.9 vs. 8.2 ± 3.2 ml/min/kg; P < 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 < 0.01). No significant difference (P > 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. Clinical Pharmacology and Therapeutics (1988) 43, 436–441; doi: 10.1038/clpt.1988.55