Influence of age on stereoselective pharmacokinetics and metabolism of hexobarbital in the rat

doi:10.1016/0047-6374(92)90033-A

Mechanisms of Ageing and Development

Volume 65, Issues 2–3, September 1992, Pages 167-175

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Abstract

The influence of age on stereoselective pharmacokinetics and in vitro metabolism of R-and S-hexobarbital was studied in the rat. After intravenous administration of the racemate, the plasma concentrations of S-hexobarbital are markedly lower than those of R-hexobarbital. For S-hexobarbital the half-life is somewhat shorter and the volume of distribution and plasma clearance is higher than for its antipode. For both enantiomers an increase in AUC and half-life, and a decrease in clearance are observed with aging. These changes occur mainly between the 3rd and the 12th month and are slightly more pronounced for R- than for S-hexobarbital, as appears from the S/R ratios. The volume of distribution shows no changes with aging. In vitro disappearance rate in 3-month-old rats in significantly higher for S- than for R-hexobarbital. There is for both enantiomers an increase in disappearance rate in 12-month-old rats as compared to younger or older rats, but this is significant only for the R-enantiomer. There are pronounced differences in the kinetics and metabolism of both hexobarbital enantiomers; changes with aging occur, but are only slightly and not always significantly more important for R- than for S-hexobarbital.

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^∗: Research Assistant of the National Fund for Scientific Research.

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Influence of age on stereoselective pharmacokinetics and metabolism of hexobarbital in the rat

Abstract

Eur. J. Pharmacol.

J. Chromatogr.

Mech. Ageing Devel.

Age-associated stereoselective alterations in hexobarbital metabolism

Clin. Pharmacol. Ther.

Age-dependent stereoselective increase in the oral clearance of hexobarbitone isomers caused by rifampicin

Br. J. Clin. Pharmacol.

Characterization and prediction of in vivo oxidative drug metabolizing enzyme activity. A re-evaluation of hexobarbital as a model substrate