C. Schweizer et al., PHARMACOKINETICS AND PHARMACODYNAMICS OF BENAZEPRIL HYDROCHLORIDE IN PATIENTS WITH MAJOR PROTEINURIA, European Journal of Clinical Pharmacology, 44(5), 1993, pp. 463-466
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.