PHARMACOKINETICS AND PHARMACODYNAMICS OF BENAZEPRIL HYDROCHLORIDE IN PATIENTS WITH MAJOR PROTEINURIA

We have investigated whether the pharmacokinetics and pharmacodynamics of the ACE inhibitor benazepril hydrochloride are altered with protei nuria by studying 8 patients with major proteinuria of different cause s who were given a single dose of 10 mg p. o. The maximum plasma conce ntration of benazepril was found between 0.5 and 2 h after dosing (med ian 1 h). Its elimination was almost complete within 6 h. Peak plasma levels of benazeprilat, the active metabolite of benazepril, were obse rved between 1 and 6 h (median 2.5 h). The elimination of benazeprilat from plasma was biphasic, with mean initial and terminal half-lives o f 3.0 and 17.3 h, respectively. On average, the pharmacokinetic parame ters of benazepril and benazeprilat in the patients did not differ fro m those in a historical control group of healthy volunteers, but inter subject variability in the AUC and half-lives of benazeprilat was grea ter in the patients. Plasma ACE was completely inhibited from 1.5 to 6 h after dosing, and at 48 h the mean inhibition was still 42 %. Plasm a renin showed substantial intersubject variation. Mean supine blood p ressure (systolic/diastolic) was reduced from baseline by a maximum of 18/13 mm Hg at 6 h. Proteinuria was diminished after benazepril in 7 patients. In conclusion, the results of this study suggest that protei nuria in the nephrotic range does not require a change in benazepril d osage.