title: Pharmacokinetics and pharmacodynamics of a novel orally active angiotensin converting enzyme inhibitor (HOE 498) in healthy subjects.
abstract: The pharmacokinetics and pharmacodynamics of the angiotensin converting enzyme inhibitor HOE 498 were investigated in 10 healthy normotensive male subjects. Serum levels of the active metabolite M 1 (dicarboxylic acid) of HOE 498 were measured by HPLC up to 14 days after a single oral dose of 10 mg HOE 498. Peak serum concentration of M 1 between 5-50 ng/ml was observed 1.5-3.0 h after administration. The serum concentration-time curve of M 1 was polyphasic and exhibited a prolonged terminal phase with a half-life of approximately 110 h. Despite the long terminal half-life M 1 could not be detected in urine later than 72 h after administration. The activity of the angiotensin converting enzyme in plasma was completely suppressed for up to 12 h, and 72 h after dosing 50% inhibition of the enzyme was still observed.
mesh_terms: D000328:Adult; D000806:Angiotensin-Converting Enzyme Inhibitors; D001643:Bridged Bicyclo Compounds / Q000097:blood / Q000378:metabolism*; D001952:Bridged-Ring Compounds / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000097:blood; D017257:Ramipril
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D001643:Bridged Bicyclo Compounds; D001952:Bridged-Ring Compounds; D007703:Peptidyl-Dipeptidase A; D017257:Ramipril