Pidlich J, Cichini G M, Reinisch W, Peck-Radosavljevic M, Renner F
Department of Gastroenterology and Hepatology, University of Vienna, Ausria.
Acta Med Austriaca. 1997;24(1):15-8.
In an open trial, the pharmacokinetics of the angiotensin converting enzyme inhibitor ramipril and its active metabolite ramiprilat were studied in 12 patients with liver cirrhosis. After a single oral dose of 5 mg ramipril plasma levels of the parent compound reached peak concentrations of 48.6 +/- 39.8 ng/ml after 0.7 +/- 0.5 h and declined rapidly to 0.7 +/- 1.2 ng/ml after 8 h. Plasma levels of ramiprilat reached peak concentrations of 3.8 +/- 2.9 ng/ml after 3.0 +/- 2.2 h, thereafter declined slowly and could be detected up to 240 h. The total recovery of ramipril and metabolites in urine within 96 h was on average 46.0 +/- 10.9% of the administered dose. Major fractions were due to diketopiperazines and glucuronides of ramipril and ramiprilat. The overall ACE inhibition was still 92.0 +/- 8.6%. In conclusion, patients with liver cirrhosis had enough capacity to metabolize and excrete the parent compound ramipril, but had not enough capacity to form ramiprilat, although enough ramiprilat was formed for sufficient ACE inhibition of about 90%. This indicates that titration of the dose should start with 5 mg or even lower doses in patients with markedly impaired liver function.
在一项开放性试验中，对12例肝硬化患者研究了血管紧张素转换酶抑制剂雷米普利及其活性代谢产物雷米普利拉的药代动力学。单次口服5mg雷米普利后，母体化合物的血浆水平在0.7±0.5小时后达到峰值浓度48.6±39.8ng/ml，并在8小时后迅速降至0.7±1.2ng/ml。雷米普利拉的血浆水平在3.0±2.2小时后达到峰值浓度3.8±2.9ng/ml，此后缓慢下降，直至240小时仍可检测到。96小时内尿液中雷米普利及其代谢产物的总回收率平均为给药剂量的46.0±10.9%。主要部分是雷米普利和雷米普利拉的二酮哌嗪和葡糖醛酸苷。总体ACE抑制率仍为92.0±8.6%。总之，肝硬化患者有足够的能力代谢和排泄母体化合物雷米普利，但形成雷米普利拉的能力不足，尽管形成的雷米普利拉足以产生约90%的充分ACE抑制作用。这表明，对于肝功能明显受损的患者，剂量滴定应从5mg甚至更低剂量开始。
