Metabolism of nilvadipine, a new dihydropyridine calcium antagonist, in rats and dogs.
1. The metabolic profiles of nilvadipine in the excreta of male rats and dogs were studied after i.v. and oral dosing. Six types of metabolites were isolated and identified from the urine of male rats and dogs or bile of rats. 2. Several metabolites were detected in the urine (12) and bile (17) of rats by two-dimensional t.l.c., after dosing with 14C-nilvadipine. The metabolic profiles in the excreta of rats and dogs were qualitatively similar but quantitative differences were observed. 3. The main metabolites were products of (i) oxidation of the 1,4-dihydropyridine ring to the corresponding pyridine, (ii) hydrolysis of the 5-isopropyl ester or 3-methyl ester group to carboxylic acid, and/or (iii) hydroxylation of the 6-methyl group or methyl group of the isopropyl ester chain. 4. Minor metabolites were products of hydrolysis from the 5-isopropyl ester to the carboxylic acid having a dihydropyridine ring, or reduction of the 3-nitro group of the phenyl moiety having a pyridine ring.
Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., Osaka, Japan.
S
S
Terashita
Y
Y
Tokuma
T
T
Fujiwara
Y
Y
Shiokawa
K
K
Okumura
H
H
Noguchi
D000818:Animals; D001646:Bile / Q000378:metabolism; D001711:Biotransformation; D002121:Calcium Channel Blockers / Q000378:metabolism* / Q000652:urine; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D004285:Dogs; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013058:Mass Spectrometry; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000652:urine; D051381:Rats; D011919:Rats, Inbred Strains; D013045:Species Specificity
D002121:Calcium Channel Blockers; C035100:nilvadipine; D009543:Nifedipine