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Kinetics and dynamics of enalapril in patients with liver cirrhosis

1989; Wiley; Volume: 45; Issue: 6 Linguagem: Inglês

10.1038/clpt.1989.87

1532-6535

Akihiro Ohnishi, Yoshimasa Tsuboi, Takashi Ishizaki, Kiyoshi Kubota, Toshiyuki Ohno, Hiroshi Yoshida, Akira Kanezaki, Teruji Tanaka,

Drug-Induced Hepatotoxicity and Protection

The pharmacokinetics and pharmacodynamics (blood pressure, heart rate, serum angiotensin-converting enzyme, and plasma renin activity) of enalapril and enalaprilat were studied after oral administration of enalapril maleate (10 mg) to seven biopsy-proven cirrhotic patients and to seven healthy subjects. The mean Cmax, AUC, and urinary excretion of enalapril and enalaprilat were greater and less (p < 0.01), respectively, and mean oral clearance of enalapril was less (p < 0.01) in the cirrhotic group than in the healthy group. However, there was no significant difference in the mean total drug (enalapril plus enalaprilat) excretion between the two groups. Blood pressure fell (p < 0.05) only at 3 or 4 hours postdose, with no change in heart rate in the two groups. Serum angiotensin-convering enzyme (ACE) decreased (p < 0.001) and plasma renin activity (PRA) increased (p < 0.05) in the two groups. The magnitude of the percentage of inhibition of ACE activity was comparable between the two groups. Serum enalaprilat concentration correlated (p < 0.001) with the percentage of inhibition of ACE activity. The results suggest that the bioactivation of enalapril to enalaprilat is considerably impaired in patients with cirrhosis but that the pharmacodynamic effects do not appear to be blunted in those patients. The mechanism and clinical implications remained unclear. Clinical Pharmacology and Therapeutics (1989) 45, 657–665; doi:10.1038/clpt.1989.87