Meyer B H, Scholtz H E, Müller F O, Luus H G, de la Rey N, Seibert-Grafe M, Eckert H G, Metzger H
Hoechst Clinic, Department of Pharmacology (G6), University of the Orange Free State, Bloemfontein, South Africa.
Eur J Clin Pharmacol. 1994;47(4):373-5. doi: 10.1007/BF00191171.
Twenty two healthy males participated in a randomised, placebo-controlled, double blind, cross-over study to investigate the influence of simvastatin on the pharmacokinetics of ramipril and its active metabolite (ramiprilat), and on the ACE-inhibiting effect of ramiprilat. During two study periods, each of 7 days, subjects received daily either simvastatin 20 mg at 19.00 h or placebo; ramipril (5 mg) was given on Day 5 of each of the periods. Plasma concentrations of ramipril and ramiprilat and ACE-activity were measured in sequential blood specimens, and ramipril and ramiprilat concentrations were measured in urine. Blood and urine collections for pharmacokinetic and pharmacodynamic assessment were made up to 72 h after the dose of ramipril. The mean AUC of ramipril for ramipril+placebo (R+P) and ramipril+simvastatin (R+S) was 22.2 and 21.3 ng.h.ml-1, respectively; for ramiprilat the corresponding figures were 61.3 and 57.6 ng.h.ml-1. The urinary excretion of ramipril+metabolites for (R+P) and (R+S) was 25.2 and 24.1% of dose. The maximum percentage inhibition of ACE-activity for (R+P) was 94.6%, and for (R+S) it was 94.1%. It is concluded that concomitant administration of simvastatin and ramipril has no clinically relevant effect on the pharmacokinetics or ACE-inhibition of the latter drug and its metabolites.
22名健康男性参与了一项随机、安慰剂对照、双盲、交叉研究，以调查辛伐他汀对雷米普利及其活性代谢产物（雷米普利拉）的药代动力学以及雷米普利拉的血管紧张素转换酶（ACE）抑制作用的影响。在两个为期7天的研究阶段中，受试者每天于19:00服用20 mg辛伐他汀或安慰剂；在每个阶段的第5天给予雷米普利（5 mg）。在连续采集的血样中测量雷米普利和雷米普利拉的血浆浓度以及ACE活性，并在尿样中测量雷米普利和雷米普利拉的浓度。在给予雷米普利剂量后长达72小时进行血样和尿样采集，用于药代动力学和药效学评估。雷米普利+安慰剂（R+P）组和雷米普利+辛伐他汀（R+S）组雷米普利的平均曲线下面积（AUC）分别为22.2和21.3 ng·h·ml⁻¹；雷米普利拉的相应数值分别为61.3和57.6 ng·h·ml⁻¹。雷米普利+代谢产物的尿排泄量在（R+P）组和（R+S）组分别为给药剂量的25.2%和24.1%。（R+P）组ACE活性的最大抑制百分比为94.6%，（R+S）组为94.1%。结论是，辛伐他汀与雷米普利联合给药对后者药物及其代谢产物的药代动力学或ACE抑制作用无临床相关影响。
