Heintz B, Verho M, Brockmeier D, Lückel G, Maigatter S, Sieberth H G, Rangoonwala B, Bender N
2nd Medical Clinic, Technical University of Aachen, Germany.
J Cardiovasc Pharmacol. 1993;22 Suppl 9:S36-42.
Thirteen patients with chronic congestive heart failure of NYHA class II-III received multiple doses (14 days) of ramipril (5 mg once daily); the concentrations of ramipril and ramiprilat in plasma, as well as ramipril, ramiprilat, glucuronides, diketopiperazine, and diketopiperazine acid in urine were measured at various times for 14 days. One patient dropped out after the first day due to hypotension and another who accidentally received another ACE inhibitor additionally was excluded, so that 11 patients completed the study. Ramipril and ramiprilat in plasma were determined by radioimmunoassay, and ramipril and its metabolites in urine were measured by gas chromatography in the laboratories of Hoechst AG. Peak concentrations of the active substance ramiprilat were reached after about 4 h and amounted to 22.3 +/- 11.1 ng/ml after the first dose, and a peak concentration of 26.6 +/- 10.0 ng/ml was observed 2.5 +/- 1.4 h on average after administration on day 14. Practically no accumulation was observed for ramiprilat; the AUD (0-24 h) values increased from 191.3 +/- 83.1 ng.h/ml for the first study day to 238.3 +/- 98.0 ng.h/ml for day 14. As expected, only very small fractions of the dose were excreted with urine as unchanged ramipril and ramipril glucuronide. Ramiprilat is excreted with urine to a larger extent than is rampiril--on average 6.6 +/- 3.0% on the first day and 12.2 +/- 3.8% on day 14. The total amount excreted increased by 34% on average, and was mainly due to an increased ramiprilat excretion.(ABSTRACT TRUNCATED AT 250 WORDS)
13例纽约心脏病协会（NYHA）心功能II - III级的慢性充血性心力衰竭患者接受了多剂量（14天）的雷米普利（每日1次，每次5毫克）治疗；在14天内的不同时间点测量了血浆中雷米普利和雷米普利拉的浓度，以及尿液中雷米普利、雷米普利拉、葡萄糖醛酸苷、二酮哌嗪和二酮哌嗪酸的浓度。1例患者因低血压在第1天后退出，另1例意外额外服用了另一种血管紧张素转换酶（ACE）抑制剂被排除，因此11例患者完成了研究。血浆中的雷米普利和雷米普利拉通过放射免疫测定法测定，尿液中的雷米普利及其代谢产物在赫斯特公司的实验室通过气相色谱法测量。活性物质雷米普利拉的峰值浓度在约4小时后达到，首剂后为22.3±11.1纳克/毫升，在第14天给药后平均2.5±1.4小时观察到峰值浓度为26.6±10.0纳克/毫升。实际上未观察到雷米普利拉有蓄积现象；药时曲线下面积（AUC，0 - 24小时）值从首个研究日的191.3±83.1纳克·小时/毫升增加到第14天的238.3±98.0纳克·小时/毫升。正如预期的那样，只有极少量的剂量以未改变的雷米普利和雷米普利葡萄糖醛酸苷形式随尿液排出。雷米普利拉随尿液排出的程度比雷米普利更大——首日平均为6.6±3.0%，第14天为12.2±3.8%。排出的总量平均增加了34%，主要是由于雷米普利拉排泄增加。（摘要截选至250字）
