Pharmacokinetics and effects of cilazapril in hypertensive patients on hemodialysis

The antihypertensive effects and pharmacokinetic properties of cilazapril, a long-acting angiotensin converting enzyme (ACE) inhibitor, were investigated in seven mildly hypertensive patients on maintenance hemodialysis (HD). A single dose (0.5mg) of cilazapril was administered orally, and plasma levels of cilazapril, cilazaprilat, an active diacid form of cilazapril, plasma renin activity, angiotensin I and II concentrations and serum ACE activity were measured on a day with HD and On a day without HD. Cilazapril reduced both systolic and diastolic blood pressure to normotensive levels. Serum ACE activity was markedly suppressed over 24hr. There were no significant changes in plasma renin activity and either angiotensin I or II concentrations after administration of 0.5mg cilazapril. Thus, the hypotensive effects of cilazapril may be due to inhibition of the tissue renin angiotensin system rather than of the circulatory system. On a day without HD, the maximum concentration (Cmax) and time required to reach the maximum concentration (Tmax) of cilazaprilat were 21.4ng/ml and 18.3h, respectively. On a day with HD, the Cmax and Tmax of cilazaprilat were 14.0ng/ml and 11.2h, respectively. The half-life of cilazaprilat was 28.6h without HD, and 3.4h during HD. These data suggest that the drug was partially removed by HD. A simulation, calculated on the basis of the above pharmacokinetic parameters, indicates that the recommended daily dose of cilazapril could be 0.5mg for hypertensive patients on whom hemodialysis is performed every other day.