Pharmacokinetics of a new angiotensin I converting enzyme inhibitor (delapril) in patients with deteriorated kidney function and in normal control subjects

Abstract

Pharmacokinetic properties of a new angiotensin-converting enzyme inhibitor, delapril (CV-3317), which converts to two active metabolites (M-1 and M-2) and one inactive metabolite (M-3) after oral administration, were investigated in six subjects with normal, 10 subjects with slight (SRF), and six subjects with markedly (MRF) deteriorated kidney function. The elimination half-life of M-1 was prolonged significantly in subjects with MRF and that of M-3 was also prolonged in subjects with SRF or MRF. The peak plasma drug concentration, time to reach peak concentration (tmax), and AUC were significantly larger in subjects with SRF and MRF than in normal subjects, except for Tmax in subjects with SRF. In M-2 and unchanged delapril, no difference was observed. The 24-hour cumulative urinary excretion of those metabolites was significantly lower in subjects with MRF than in normal subjects. Plasma angiotensin-converting enzyme activity, suppressed at 4 hours in all subjects, remained significantly low in patients with MRF at 24 hours. Blood pressure was reduced more in subjects with chronic renal failure. It was concluded that delapril is excreted mainly through the kidney and its pharmacodynamics and biologic effects are affected by the renal dysfunction.