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- W2105759780 abstract "1. The metabolic fate of nicarpidine hydrochloride by rats, dogs and monkeys in vitro has been compared with previously reported in vivo studies. 2. The rate of metabolism of the drug in rat liver was 1.76 mumol/g tissue per 20 min, while the values in the intestine, kidney, lung and blood were less than 0.1 mumol/g tissue per 20 min, suggesting that the first-pass effect observed in vivo was due mainly to metabolism of the drug in the liver. 3. The rates of liver metabolism were 1.76, 0.45 and 0.55 mumol/g tissue per 20 min in rats, dogs and monkeys, respectively. This species difference correlates well with the differences in plasma clearance values, which were 197, 37 and 27 ml/min per kg in rats, dogs and monkeys, respectively, after i.v. administration of nicardipine hydrochloride (0.4 mg/kg). 4. Urinary metabolites were qualitatively similar, but the proportions of each were slightly different, among rats, dogs, monkeys and humans. The most abundant urinary metabolite was derived from debenzylation of the N-benzyl-N-methylaminoethyl ester side-chain in dogs and humans, and from hydrolysis of the same side-chain to the carboxylic acid, together with oxidation of the dihydropyridine nucleus to pyridine, in rats and monkeys. The metabolites produced in vitro were also qualitatively similar in the animal species examined. 5. More than 90% of the drug was reversibly bound to the plasma protein at 0.1 microgram/ml in the three animal species and humans. The extent of binding decreased with increased drug concentration in rats and humans, but not in dog and monkeys." @default.
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- W2105759780 title "Metabolic fate of nicardipine hydrochloride, a new vasodilator, by various species<i>in vitro</i>" @default.
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- W2105759780 doi "https://doi.org/10.3109/00498258009033822" @default.
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