Comparative pharmacokinetics of nicardipine hydrochloride, a new vasodilator, in various species

Abstract

The pharmacokinetics of a new potent vasodilator, 2-(N-benzyl-N-methylamino)-ethyl methyl 2,6-dimethyl-4-(m-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate hydrochloride (nicardipine hydrochloride), were studied after oral and i.v. dosage to rats, dogs, rhesus monkeys and humans. The plasma half-life [t1/2] and volume of distribution in humans after i.v. administration did not change with dosage in clinical range. In rats and dogs these parameters increased with higher doses, probably because of the potent vasodilative effect of the drug. The plasma clearance in dogs and humans was not affected by dosage, but in rats tended to increase slightly with higher doses. Systemic availability after oral administration was low in spite of excellent absorption, indicating a marked 1st-pass effect. Increased systemic availability with increased dose indicates that the metabolic activity of the liver may become partly saturated with the durg or its metabolites. Disappearance of the drug from the plasma after i.v. administration was fastest in rats > dogs .apprxeq. monkeys > humans. The terminal T1/2 of the drug after i.v. administration to humans was .apprx. 1 h.