PHARMACOKINETICS AND HEMODYNAMIC-EFFECTS OF THE ANGIOTENSIN-CONVERTING ENZYME-INHIBITOR CILAZAPRIL IN HYPERTENSIVE PATIENTS WITH NORMAL ANDIMPAIRED RENAL-FUNCTION

1 The pharmacokinetic and pharmacodynamic properties of the angiotensi n converting enzyme (ACE) inhibitor cilazapril were studied in 30 hype rtensive patients with various degrees of renal function. 2 After a si ngle oral dose, apparent cilazaprilat clearance was dependent on renal function being 16.0 +/- 3.0, 11.1 +/- 3.0, 8.7 +/- 3.7 and 6.7 +/- 2. 1 l h(-1) (means +/- s.d.) in patients with creatinine clearances (CL( cr)) of > 100, 41-100, 21-40, and 8-20 ml min(-1), respectively. 3 Dur ing 11 weeks of treatment with cilazapril, doses were adjusted to the CL(cr) and varied from 0.5 to 5.0 mg once daily. At 24 h after drug ad ministration a clear antihypertensive response was seen only in the lo w clearance groups (CL(cr) <40 ml min(-1)). In contrast, and despite h igher once daily dosages, the decline of mean arterial pressure was sm all and cilazaprilat concentrations after 24 h were lower in the high clearance groups. 4 This study demonstrates that chronic once daily tr eatment with cilazapril is effective in patients with impaired renal f unction at dosages adjusted to creatinine clearance. No accumulation w as seen. Since cilazaprilat clearance was high in the high creatinine clearance groups, a clear antihypertensive response in these groups wa s only seen at 3 h after drug administration.