Interspecies comparison of the metabolic pathways of perindopril, a new angiotensin-converting enzyme (ACE) inhibitor.
1. The metabolism of perindopril (non-thiol angiotensin-converting enzyme inhibitor) was studied in rat, dog and monkey after single oral and i.v. administration of 14C-perindopril, and in man after a single oral dose. 2. Six biotransformation products of perindopril from urine, faecal and plasma samples (bile only for rats) were identified. 3. The main route of biotransformation in all species is the hydrolysis of the carboxylic ethyl ester side-chain, with the formation of perindoprilate, the active metabolite. 4. A minor route of biotransformation led to the acyl glucuronides of perindopril and perindoprilate. 5. Internal dehydration of perindopril and perindoprilate into cyclic lactam structures occurs. This route of metabolism is of minor importance except in humans.
Grislain
L
L
Bio-Pharmacie Servier, Orleans, France.
Mocquard
M T
MT
Dabe
J F
JF
Bertrand
M
M
Luijten
W
W
Marchand
B
B
Resplandy
G
G
Devissaguet
M
M
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000493:pharmacokinetics*; D000818:Animals; D001711:Biotransformation; D004285:Dogs; D005243:Feces / Q000737:chemistry; D005260:Female; D005965:Glucuronates / Q000378:metabolism; D006801:Humans; D006868:Hydrolysis; D007211:Indoles / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D008253:Macaca mulatta; D008297:Male; D015394:Molecular Structure; D020913:Perindopril; D051381:Rats; D011919:Rats, Inbred Strains; D013045:Species Specificity
D000806:Angiotensin-Converting Enzyme Inhibitors; D005965:Glucuronates; D007211:Indoles; D020913:Perindopril