血栓素A-2受体阻滞剂BM 13.177的药代动力学和药效学特征。

The pharmacokinetic and pharmacodynamic profiles of the thromboxane A-2 receptor blocker BM 13.177.

作者信息

Patscheke H, Staiger C, Neugebauer G, Kaufmann B, Strein K, Endele R, Stegmeier K

出版信息

Clin Pharmacol Ther. 1986 Feb;39(2):145-50. doi: 10.1038/clpt.1986.25.

DOI:10.1038/clpt.1986.25

Abstract

The pharmacokinetics and pharmacodynamics of BM 13.177 were investigated in eight healthy men who received a single oral dose of 800 mg on the first day and seven equal doses in 8-hour intervals on the second to fourth days. Pharmacodynamic effects were measured ex vivo by the testing of platelet functions such as shape change, aggregation, and [3H]serotonin release. The maximum serum concentration of 6.6 or 6.7 mg/L was achieved within 1.6 hours after the first dose and within 1.5 hours after multiple doses, respectively. Afterwards, BM 13.177 was eliminated in urine with a terminal elimination t1/2 of 0.84 or 1.0 hours after single and multiple dosing, respectively. The inhibition of platelet function showed the same close correlation with the serum concentrations of BM 13.177 after single and after multiple doses. Apparently, BM 13.177 induces neither refractoriness to BM 13.177 nor desensitization of the platelet thromboxane receptor. Because BM 13.177 was also well tolerated without subjective or objective side effects, this drug appears to be useful in evaluating the clinical benefit of thromboxane receptor blockade.

摘要

在8名健康男性中研究了BM 13.177的药代动力学和药效学。第一天他们接受了800毫克的单次口服剂量，在第二天至第四天以8小时间隔接受了7次等量剂量。通过测试血小板功能（如形状变化、聚集和[3H]5-羟色胺释放）进行离体药效学效应测量。首次给药后1.6小时内和多次给药后1.5小时内分别达到最大血清浓度6.6或6.7毫克/升。此后，BM 13.177经尿液消除，单次给药和多次给药后的终末消除半衰期分别为0.84或1.0小时。单次给药和多次给药后，血小板功能抑制与BM 13.177的血清浓度均呈现相同的密切相关性。显然，BM 13.177既不会诱导对BM 13.177的耐受性，也不会使血小板血栓素受体脱敏。由于BM 13.177耐受性良好，无主观或客观副作用，该药物似乎可用于评估血栓素受体阻断的临床益处。