Whitehead E M, Walters G E, Williams P E, Johnston G D
Department of Therapeutics and Pharmacology, Queen's University, Belfast, Northern Ireland.
Br J Clin Pharmacol. 1989 Jun;27(6):873-5. doi: 10.1111/j.1365-2125.1989.tb03453.x.
The pharmacokinetics of 1 mg, 2 mg and 4 mg of cilazaprilat administered intravenously were determined in a group of eight volunteers. The fall in plasma concentration was polyphasic. Elimination was predominantly by renal excretion of the unchanged drug. The mean renal clearance values following 1 mg, 2 mg and 4 mg doses were 5.3 +/- 0.5, 8.1 +/- 0.5, and 9.8 +/- 0.5 l h-1 and plasma clearances were 7.8 +/- 0.5, 10.4 +/- 0.5 and 11.8 +/- 0.6 l h-1, respectively. Thus, plasma and renal clearances were dose dependent. ACE inhibition was greater than 82% for the first 4 h and about 55% at 24 h, after all three doses. There were no significant haemodynamic effects at any dose.
在一组8名志愿者中测定了静脉注射1毫克、2毫克和4毫克西拉普利拉的药代动力学。血浆浓度下降呈多相性。消除主要是通过原形药物的肾脏排泄。1毫克、2毫克和4毫克剂量后的平均肾脏清除率分别为5.3±0.5、8.1±0.5和9.8±0.5升/小时,血浆清除率分别为7.8±0.5、10.4±0.5和11.8±0.6升/小时。因此,血浆清除率和肾脏清除率均呈剂量依赖性。所有三种剂量给药后,前4小时ACE抑制率均大于82%,24小时约为55%。任何剂量均未产生显著的血流动力学效应。