Hildebrandt A G, Roots I, Speck M, Saalfrank K, Kewitz H
Eur J Clin Pharmacol. 1975 Jun 13;8(5):327-36. doi: 10.1007/BF00562658.
The 24 h urinary excretion of 6beta-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 6beta-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 less than 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.
在19名健康男性志愿者中，测定了6β-羟基皮质醇和D-葡糖醛酸的24小时尿排泄量、氨基比林的血浆半衰期和总清除率，以及血清γ-谷氨酰转肽酶活性。该研究采用双盲法进行，作为每日服用6毫克氯马斯汀、300毫克苯巴比妥或安慰剂期间及之后微粒体药物代谢酶诱导试验。苯巴比妥组（诱导标准组）6β-羟基皮质醇和D-葡糖醛酸的尿排泄量显著增加。服用氯马斯汀或安慰剂后未观察到变化。苯巴比妥还缩短了氨基比林的半衰期，但氯马斯汀或安慰剂对其无影响。γ-谷氨酰转肽酶活性仅在苯巴比妥组中升高。氨基比林的消除常数k2与用药前葡糖醛酸的排泄量相关（p<0.05）。结果表明，这些试验在测定苯巴比妥诱导微粒体酶方面具有诊断价值。服用氯马斯汀后未观察到类似变化，这意味着在实验条件下该活性未被诱导。
