Evaluation ofin vivo parameters of drug metabolizing enzyme activity in man after administration of clemastine, phenobarbital or placebo
- 1 January 1975
- journal article
- clinical trial
- Published by Springer Nature in European Journal of Clinical Pharmacology
- Vol. 8 (5), 327-336
- https://doi.org/10.1007/bf00562658
Abstract
Summary The 24 h urinary excretion of 6β-hydroxycortisol and D-glucaric acid, the plasma half-lives and total clearances of aminopyrine, and serum gamma-glutamyl-transpeptidase activity have been measured in nineteen healthy male volunteers. The study was done double blind and was conducted as a test of induction of microsomal drug metabolizing enzymes during and after daily doses of 6 mg clemastine, 300 mg phenobarbital or a placebo. The urinary excretion of 6β-hydroxycortisol and D-glucaric acid was significantly increased in the phenobarbital group, the standard for induction. No changes were observed after treatment with clemastine or placebo. Phenobarbital also reduced the half life of aminopyrine, but it was not affected by clemastine or placebo. Gamma-glutamyl-transpeptidase activity increased only in the phenobarbital group. The elimination constant k2 of aminopyrine and the excretion of glucaric acid in the pre-medication period were correlated (p<0.05). The results indicate that the tests were of diagnostic value in determination of microsomal enzyme induction by phenobarbital. Failure to observe similar changes after treatment with clemastine imply failure of induction of this activity under the experimental conditions.Keywords
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