Kinetics, safety, and efficacy of ramipril after long-term administration in hemodialyzed patients

被引:10
作者
Fillastre, JP
Baguet, JC
Dubois, T
Vauquier, J
Godin, M
Legallicier, B
Luus, HG
delaRey, N
Carcone, N
Genthon, R
机构
[1] CHU ROUEN,DEPT NEPHROL,ROUEN,FRANCE
[2] CHU CLERMONT FERRAND,DEPT NEPHROL,CLERMONT FERRAND,FRANCE
[3] RED CROSS HOSP,HAEMODIALYSIS CTR,BOIS GUILLAUME,FRANCE
[4] UNIV ORANGE FREE STATE,DEPT PHARMACOL,DIV BIOMETRY,BLOEMFONTEIN,SOUTH AFRICA
[5] LABS HOECHST,DEPT MED,PARIS,FRANCE
关键词
ramipril; hemodialysis; angiotensin; converting enzyme inhibitors; ramiprilat; pharmacokinetics; pharmacodynamics;
D O I
10.1097/00005344-199602000-00014
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
We studied the efficacy and safety of ramipril and the kinetics of its active moiety ramiprilat in 12 hypertensive patients receiving regular hemodialysis, after a single dose and after long-term (28 days) administration. Patients received 2.5 mg ramipril after each hemodialysis. On days 1 and 29, ramipril was administered 4 h before the hemodialysis and serial blood samples were obtained for 9 h for determination of pharmacokinetic parameters. Tolerability was good, and all patients completed the study, There was a high degree of angiotensin-converting enzyme (ACE) inhibition throughout the study. Ramipril had a clear-cut antihypertensive effect. Long-term administration of ramipril did not modify the time to peak ramiprilat concentration, but increased the mean maximal concentration significantly: 20.2 +/- 12.7 vs. 10.4 +/- 7.1 ng . ml(-1). The mean accumulation ratio was 2.2. Ramiprilat hemodialysis clearance was 31.7 ml/min (range 4.2-64.9 ml/min) on day 1 and 21.0 ml/min (range 7.9-56.5 ml/min) on day 29. Ramipril 2.5 mg, administered after hemodialysis, appears to be safe and effective in hypertensive patients receiving periodic hemodialysis. Despite an increase in ramiprilat concentration from day 1 to day 29, the steady state was reached. We describe the role of nonrenal clearance of ramiprilat.
引用
收藏
页码:269 / 274
页数:6
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