Antihypertensive Effects and Pharmacokinetics of Temocapril, an Angiotensin Converting Enzyme Inhibitor with Preferential Biliary Excretion, in Patients with Impaired Renal Function

Since the discovery of captopril, the first angiotensin converting enzyme (ACE) inhibitor, by Ondetti et al. in 1977, many ACE inhibitors have been developed (Hui et al. 1991; Ondetti et al. 1977). However, almost all ACE inhibitors currently available, with the exception of fosinopril (Gavras & Gavras 1988), are excreted mainly in the urine through the kidneys. Therefore, in order to prevent an unnecessary increase in plasma concentrations in patients with impaired renal function, careful attention should be paid to the dose, the dose interval and the choice of drug (Oizumi et al. 1988; Suzuki et al. 1992). Temocapril is a novel ACE inhibitor that has been shown in experimental animals and man to be primarily excreted in faeces through the bile (Nakashima et al. 1992; Oguchi et al. 1993). A pharmacokinetic study of a single dose of temocapril has been performed in patients with impaired renal function (Nakashima et al. 1992; Oguchi et al. 1993), and showed that the pharmacokinetics of the drug were similar to those in patients with normal renal function. Another pharmacokinetic study has shown that temocapril is eliminated preferentially through the biliary route and that its bioactivity is hardly affected in patients with liver dysfunction (Furuta et al. 1993). The present study was conducted to evaluate the pharmacokinetics and antihypertensive effects of temocapril in hypertensive patients with severely impaired renal function during administration of temocapril for 7 consecutive days.