KINETICS, SAFETY, AND EFFICACY OF RAMIPRIL AFTER LONG-TERM ADMINISTRATION IN HEMODIALYZED PATIENTS

We studied the efficacy and safety of ramipril and the kinetics of its active moiety ramiprilat in 12 hypertensive patients receiving regula r hemodialysis, after a single dose and after long-term (28 days) admi nistration. Patients received 2.5 mg ramipril after each hemodialysis. On days 1 and 29, ramipril was administered 4 h before the hemodialys is and serial blood samples were obtained for 9 h for determination of pharmacokinetic parameters. Tolerability was good, and all patients c ompleted 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 m ean maximal concentration significantly: 20.2 +/- 12.7 vs. 10.4 +/- 7. 1 ng . ml(-1). The mean accumulation ratio was 2.2. Ramiprilat hemodia lysis clearance was 31.7 ml/min (range 4.2-64.9 ml/min) on day 1 and 2 1.0 ml/min (range 7.9-56.5 ml/min) on day 29. Ramipril 2.5 mg, adminis tered after hemodialysis, appears to be safe and effective in hyperten sive patients receiving periodic hemodialysis. Despite an increase in ramiprilat concentration from day 1 to day 29, the steady state was re ached. We describe the role of nonrenal clearance of ramiprilat.