Metabolic fate of the new angiotensin-converting enzyme inhibitor imidapril in animals. 2nd communication: tissue distribution and whole-body autoradiography of imidapril in rats.
Tissue distribution, whole-body autoradiography and metabolic profiles in selected tissues of imidapril hydrochloride ((-)-(4S)-3-[(2S)-2-[[(1S)-1-ethoxycarbonyl-3- phenylpropyl]amino]propionyl]-1-methyl-2-oxoimidazolidine-4-carboxylic acid hydrochloride, imidapril, TA-6366, CAS 89396-94-1) were studied in male and female rats after oral and intravenous administration of [N-methyl-14C]-imidapril (1 and 5 mg/kg) or [alanine-3-14C]-imidapril (1 mg/kg). After oral administration of [N-methyl-14C]-imidapril, radioactivity was distributed relatively rapidly to all tissues, except for the central nervous system. Maximum concentrations in most tissues were observed at 30 min to 1 h after dosing. Concentrations greater than those in the plasma were found in the liver, kidney and particularly in the lung except for the gastrointestinal contents. The elimination from the lung was relatively slow (t1/2: ca. 28 h). At 96 h after dosing, there was no evidence of remaining radioactivity in any tissues, except for the lung and kidney. No gender-related differences in the tissue distribution profile of radioactivity were observed in the whole-body autoradiogram. After intravenous administration, the distribution pattern of radioactivity was similar to the results of oral administration, except for the gastrointestinal contents. There was no specific binding of drug-related compounds to melanin-containing tissues such as the hair follicles and the uveal tract of the eye in the pigmented rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Yamada
Y
Y
Research Laboratory of Drug Metabolism, Tanabe Seiyaku Co., Ltd. Saitama, Japan.
Endo
M
M
Kohno
M
M
Otsuka
M
M
Takaiti
O
O
D000284:Administration, Oral; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000493:pharmacokinetics*; D000818:Animals; D001345:Autoradiography; D005260:Female; D006207:Half-Life; D007093:Imidazoles / Q000493:pharmacokinetics*; D048289:Imidazolidines; D007275:Injections, Intravenous; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D014018:Tissue Distribution
D000806:Angiotensin-Converting Enzyme Inhibitors; D007093:Imidazoles; D048289:Imidazolidines; C065166:imidapril