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The influence of age and gender on the stereoselective metabolism and pharmacokinetics of mephobarbital in humans
Author(s) -
Hooper Wayne D,
Qing Mi Sui
Publication year - 1990
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.1990.207
Subject(s) - pharmacokinetics , stereoselectivity , enantiomer , physiology , disposition , metabolism , cytochrome p450 , young adult , age groups , clinical pharmacology , pharmacology , medicine , endocrinology , chemistry , psychology , demography , stereochemistry , biochemistry , social psychology , sociology , catalysis
In this clinical investigation, four groups of subjects (eight young women and eight young men [age range, 18 to 25 years], and eight elderly women and eight elderly men [>60 years of age]) received single oral doses (400 mg) of racemic mephobarbital. The apparent total body clearance of R ‐mephobarbital was much greater and the elimination half‐life was much shorter in the young men compared with the other three groups. This enantiomer displayed an age‐dependent gender effect and a gender‐dependent age effect in its metaoblism. The apparent total body clearance of the S ‐enantiomer was much lower than that of the R ‐enantiomer in all subjects and did not differ between subject groups, although the elimination half‐life was slightly but signifiantly shorter in young males. A consequence of these enantiomeric differences was an apparently enhanced stereoselectivity in the metabolism of mephobarbital in young men. These substantial influences of age and gender on the stereoselective disposition of mephobarbital are consistent with recent findings concerning the expression and regulation of cytochrome P450 enzymes. Clinical Pharmacology and Therapeutics (1990) 48 , 633–640; doi: 10.1038/clpt.1990.207