SINGLE-DOSE PHARMACOKINETICS OF TEMOCAPRIL, AN ACE-INHIBITOR WITH PREFERENTIAL BILIARY-EXCRETION, IN DIALYSIS PATIENTS

The single dose pharmacokinetics of temocapril, a novel prodrug type a ngiotensin converting enzyme (ACE) inhibitor with preferential biliary excretion, were evaluated in 6 patients maintained on haemodialysis a nd in 1 patient on continuous ambulatory peritoneal dialysis (CAPD). I n a crossover design, each haemodialysis patient received a single ora l dose of temocapril 1mg after breakfast on two occasions, on dialysis and nondialysis days, at an interval of 1 week. The CAPD patient rece ived a single oral dose of temocapril 1mg. Plasma concentrations of te mocapril and its active metabolite (diacid) and ACE activity were dete rmined after drug administration. Area under the plasma concentration- time curves (AUC) in haemodialysis patients on the nondialysis day wer e significantly greater than those in patients with normal renal funct ion who were used as a reference (p < 0.01). Other pharmacokinetic par ameters such as maximum plasma drug concentration (C(max)), biological half-life (t1/2) and time to reach C(max), (t(max)) were not signific antly different between the 2 groups. 24 hours after administration, t he ACE inhibitions in haemodialysis patients were significantly higher than those in patients with normal renal function. There were no othe r significant differences between the 2 groups. The peak level of diac id (C(max)) in haemodialysis patients on the nondialysis day was signi ficantly greater than that on the dialysis day (p < 0.05). Other pharm acokinetic parameters such as AUC, t1/2 and t(max). were not significa ntly different between these 2 days. These parameters in die CAPD pati ent were similar to those in the haemodialysis patients on dialysis da y. The results suggest that the elimination route of temocapril is mai nly via the biliary route, but is partially a route permeated through a dialyser membrane or peritoneal membrane. It is suggested that temoc april is preferable to ACE inhibitors with renal elimination in the tr eatment of patients with hypertension undergoing dialysis.