The angiotensin-converting enzyme (ACE)-inhibitor, cilazapril, is converted to its active metabolite, cilazaprilat, by ester hydrolysis in the liver. The pharmacokinetics and pharmacodynamics of a single 1 mg oral dose of cilazapril were investigated in 10 healthy volunteers and in 9 cirrhotic patients with compensated cirrhosis and portal hypertension. A significantly increased mean plasma peak concentration (40.0 +/- 13.6 ng/ml vs. 25.5 +/- 7.9 ng/ml; p < 0.05) and a decreased apparent oral clearance (7.8 +/- 6.0 l/h vs. 16.4 +/- 5.4 l/h; p < 0.05) of cilazapril were found in cirrhotic patients compared to healthy volunteers. The plasma concentration of cilazaprilat declined in 2 phases. In both phases the plasma half-life was significantly longer in patients with cirrhosis (1st phase: 2.5 +/- 0.8 h vs. 1.7 +/- 0.6 h; p < 0.05; 2nd phase: 46.2 +/- 16.6 h vs. 28.8 +/- 4.7 h; p < 0.001). Consequently, cilazaprilat concentrations at 24 h were higher in patients than in volunteers (1.42 +/- 0.33 ng/ml vs. 0.87 +/- 0.14 ng/ml; p < 0.001). The predose activity of the ACE (26.3 +/- 7.3 U/l vs. 16.8 +/- 4.5 U/l; p < 0.005) and plasma renin activity (3.3 +/- 3.2 ng/ml/h vs. 1.4 +/- 1.0 ng/ml/h) were higher in patients than in volunteers. Maximum ACE-inhibition occurred at similar times in patients (2.7 h) and volunteers (2.3 h). Maximum ACE-inhibition was slightly higher in volunteers (94.6%) than in patients (90.6%). At later time points (> 24 h), however, ACE-inhibition was more pronounced in patients (at 72 h: 39.6 +/- 6.9% vs. 23.5 +/- 8.2%; p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)