Kobayashi H, Kobayashi S, Inoue A, Oka T, Nakamizo N
Pharmaceutical Research Laboratories, Kyowa Hakko Kogyo Co., Ltd., Shizuoka, Japan.
Arzneimittelforschung. 1988 Nov;38(11A):1750-3.
(+/-) - (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.
（±）-（R*）-2,6-二甲基-4-（间硝基苯基）-1,4-二氢吡啶-3,5-二羧酸（R*）-1-苄基-3-哌啶酯甲酯盐酸盐（盐酸贝尼地平，KW-3049）目前正作为一种抗高血压和抗心绞痛药物进行研发。在大鼠和犬身上进行的口服和静脉给药后的药代动力学研究表明，KW-3049从胃肠道迅速吸收，在组织中分布适度且消除相对较快。口服给药后，在大鼠和犬中均观察到生物利用度随剂量增加呈非线性。静脉给药后，雌性和雄性大鼠的药物处置情况相似。在一些血浆样本中还测定了KW-3049二氢吡啶环的氧化产物。其吡啶代谢物的浓度率在大鼠和犬中分别占KW-3049加吡啶代谢物总浓度的0%至30%和0%至23%。
