Krause W, Schubert M, Totzek M
Prostaglandins Leukot Med. 1983 Jul;11(3):325-38. doi: 10.1016/0262-1746(83)90044-6.
The pharmacokinetics of ZK 36 374 after intravenous, oral and topical administrations to female monkeys has been investigated using tritium-labelled drug. Following intravenous injection of 2 and 200 microgram/kg a triphasic decline in the plasma levels of labelled compounds was observed with half-lives of 45 min, 4.3 h and 1.7 d. The half-life of the unchanged drug was 13 min. Almost 10% of an oral dose of 200 microgram/kg were bioavailable exhibiting maximum plasma levels of 5.7 +/- 3.6 ng/ml. The drug was totally metabolized and excreted mainly with the urine in the form of more than 10 metabolites. Following topical application of 1 mg, 5.5 +/- 2.2% of the dose was percutaneously absorbed using a TRIS-buffered solution of ZK 36 374 and 1.3 +/- 0.2% was absorbed applying an ethanolic solution of the drug. The plasma levels of labelled compounds were practically constant during the whole observation period of 36 hours.
已使用氚标记的药物对雌性猴子静脉注射、口服和局部给药后ZK 36 374的药代动力学进行了研究。静脉注射2和200微克/千克后，观察到标记化合物的血浆水平呈三相下降，半衰期分别为45分钟、4.3小时和1.7天。原形药物的半衰期为13分钟。口服剂量200微克/千克时，近10%的药物具有生物利用度，血浆最高水平为5.7±3.6纳克/毫升。该药物完全代谢，主要以10多种代谢物的形式随尿液排泄。局部应用1毫克后，使用ZK 36 374的TRIS缓冲溶液时，5.5±2.2%的剂量经皮吸收，使用该药物的乙醇溶液时，1.3±0.2%的剂量被吸收。在整个36小时的观察期内，标记化合物的血浆水平实际上保持恒定。
