van Giersbergen Paul L M, Bodin Frédéric, Dingemanse Jasper
Actelion Pharmaceuticals Ltd, Clinical Pharmacology, Gewerbestrasse 18, 4123 Allschwil, Switzerland.
Eur J Clin Pharmacol. 2002 Jul;58(4):243-5. doi: 10.1007/s00228-002-0459-0. Epub 2002 May 23.
To investigate in 12 healthy subjects the pharmacokinetics and tolerability of tezosentan, an endothelin receptor antagonist, when given concomitantly with cyclosporin.
Tezosentan was infused at a dose of 6.25 mg/h and 25 mg/h for 6 h either alone or following a single dose of 400 mg cyclosporin. Blood and urine samples were collected for pharmacokinetic determinations. Vital signs, electrocardiogram, adverse events, and clinical laboratory parameters were monitored to assess tolerability.
Concomitant cyclosporin resulted in a fourfold increase in the exposure to tezosentan. Tezosentan alone was well tolerated. In combination with cyclosporin, and at both doses, all subjects reported headache, hot flushes and nausea/vomiting, some of which were of severe intensity.
The poor tolerability of the combination of cyclosporin and tezosentan is not correlated with the plasma concentrations of tezosentan.
在12名健康受试者中研究内皮素受体拮抗剂替唑生坦与环孢素合用时的药代动力学及耐受性。
替唑生坦以6.25mg/h和25mg/h的剂量输注6小时，分别单独给药或在单次给予400mg环孢素后给药。采集血样和尿样进行药代动力学测定。监测生命体征、心电图、不良事件及临床实验室参数以评估耐受性。
环孢素合用使替唑生坦的暴露量增加了四倍。单独使用替唑生坦耐受性良好。与环孢素合用时，在两个剂量下，所有受试者均报告有头痛、潮热及恶心/呕吐，其中一些症状严重。
环孢素与替唑生坦合用耐受性差与替唑生坦的血浆浓度无关。
