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.
Kobayashi
H
H
Pharmaceutical Research Laboratories, Kyowa Hakko Kogyo Co., Ltd., Shizuoka, Japan.
Kobayashi
S
S
Inoue
A
A
Oka
T
T
Nakamizo
N
N
D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity; D004285:Dogs; D005260:Female; D006207:Half-Life; D007275:Injections, Intravenous; D007408:Intestinal Absorption; D008297:Male; D009543:Nifedipine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000633:toxicity; D010084:Oxidation-Reduction; D051381:Rats; D011919:Rats, Inbred Strains; D014018:Tissue Distribution
D002121:Calcium Channel Blockers; C050883:benidipine hydrochloride; D009543:Nifedipine