de Mey C, Meineke I, Wesche H
Eur J Drug Metab Pharmacokinet. 1987 Jan-Mar;12(1):65-9. doi: 10.1007/BF03189863.
Temelastine (SK&F 93944) is a novel histamine H1-receptor antagonist with a high degree of protein binding and predominant hepatic elimination. The pharmacokinetics of antipyrine were assessed in eight male normal subjects after single oral doses of 10 mg/kg antipyrine, administered prior to chronic dosing with temelastine 100 mg twice daily for 2 weeks, and 48 hours after the last dose of temelastine. After the first dose of antipyrine the mean maximum plasma concentration (Cmax) was 78.3 mumol/l (range: 60.3 to 95.8), the mean AUC (0-infinity) was 1330 mumol.h/l (range: 1030 to 2074), the mean apparent terminal disposition rate constant K was 0.0656 h-1 (range: 0.0428 to 0.0769) and the mean residence time (MRT) was 16.7 h on average (range: 14.4 to 24.1). After the second dose the mean Cmax, AUC (0-infinity) and MRT had slightly increased by on average 11, 5 and 7% respectively whereas the mean K had decreased by 9%. None of the differences between the means of the log-transformed parameters for second-first dose reached statistical significance. Temelastine therefore did not appear to induce hepatic oxidative enzyme activity in man, as judged by antipyrine as a model substance.
替美斯汀（SK&F 93944）是一种新型组胺H1受体拮抗剂，具有高度的蛋白结合率且主要经肝脏消除。在8名男性正常受试者中，于每日两次口服100 mg替美斯汀进行2周的长期给药之前，以及最后一剂替美斯汀给药后48小时，单次口服10 mg/kg安替比林，评估安替比林的药代动力学。首次服用安替比林后，平均最大血浆浓度（Cmax）为78.3 μmol/l（范围：60.3至95.8），平均AUC（0-∞）为1330 μmol·h/l（范围：1030至2074），平均表观终末处置速率常数K为0.0656 h-1（范围：0.0428至0.0769），平均驻留时间（MRT）平均为16.7小时（范围：14.4至24.1）。第二次给药后，平均Cmax、AUC（0-∞）和MRT分别平均略有增加，分别为11%、5%和7%，而平均K下降了9%。第二次与第一次给药后对数转换参数均值之间的差异均未达到统计学显著性。因此，以安替比林作为模型物质判断，替美斯汀似乎并未诱导人体肝脏氧化酶活性。
