Pharmacokinetic study of benidipine hydrochloride in rats and dogs

(+/-) - (R*) - 2,6-Dimethyl-4-(m-nitrophenyl)-1,4-dihydropyridine - 3, 5-dicarboxylic acid (R*)-1-benzyl-3-piperidinyl ester, methyl ester hydrochloride (benidipine hydrochloride, KW-3049) is presently under development as an anti-hypertensive and antianginal agent. A pharmacokinetic study in rat and dog after oral and intravenous administrations revealed that KW-3049 was rapidly absorbed from the gastrointestinal tract, distributed into tissues moderately and comparatively quickly eliminated. After oral administration, non-linearity of bioavailability with increment of doses was observed in both rat and dog. Female and male rats showed similar drug disposition after intravenous administration. Oxidation product of KW-3049 dihydropyridine ring was also measured in some plasma samples. The concentration rates of its pyridine metabolite accounted for 0 to 30% and 0 to 23% of the combined concentration of KW-3049 plus the pyridine metabolite in rat and dog.