title: Pharmacokinetics and pharmacodynamics of benazepril hydrochloride in patients with major proteinuria.
abstract: We have investigated whether the pharmacokinetics and pharmacodynamics of the ACE inhibitor benazepril hydrochloride are altered with proteinuria by studying 8 patients with major proteinuria of different causes who were given a single dose of 10 mg p.o. The maximum plasma concentration of benazepril was found between 0.5 and 2 h after dosing (median 1 h). Its elimination was almost complete within 6 h. Peak plasma levels of benazeprilat, the active metabolite of benazepril, were observed between 1 and 6 h (median 2.5 h). The elimination of benazeprilat from plasma was biphasic, with mean initial and terminal half-lives of 3.0 and 17.3 h, respectively. On average, the pharmacokinetic parameters of benazepril and benazeprilat in the patients did not differ from those in a historical control group of healthy volunteers, but intersubject variability in the AUC and half-lives of benazeprilat was greater 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%. Plasma renin showed substantial intersubject variation. Mean supine blood pressure (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 proteinuria in the nephrotic range does not require a change in benazepril dosage.
authors.affiliation: Department of Medicine, University of Heidelberg, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Schweizer
authors.forename: G
authors.initials: G
authors.lastname: Kaiser
authors.forename: W
authors.initials: W
authors.lastname: Dieterle
authors.forename: J
authors.initials: J
authors.lastname: Mann
mesh_terms: D000328:Adult; D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D000959:Antihypertensive Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D001552:Benzazepines / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D008297:Male; D008875:Middle Aged; D011507:Proteinuria / Q000378:metabolism*
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D001552:Benzazepines; C052133:benazeprilat; C044946:benazepril