Kobayashi H, Ohishi T, Nishiie H, Kobayashi S, Inoue A, Oka T, Nakamizo N
Pharmaceutical Research Laboratories, Kyowa Hakko Kogyo Co., Ltd., Shizuoka, Japan.
Arzneimittelforschung. 1988 Nov;38(11A):1742-6.
(+/-)-(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) has been developed as antihypertensive and antianginal agent. The absorption, distribution and excretion were investigated after single oral administration of 14C-labeled KW-3049 using Wistar rats and beagle dogs. The results were summarized as follows: 1. After oral administration of 14C-KW-3049 to rats, the plasma radioactivity reached the maximum at 0.5 h, showed the second peak at 4 h and decreased biphasically with the biological half-lives of about 6 h and 38 h. 2. After oral administration of 14C-KW-3049 to dogs, the plasma radioactivity reached the maximum at 1 h and decreased biphasically with the biological half-lives of about 2 h and 25 h. 3. After oral administration to rats and dogs, the excretion of the radioactivity in feces and urine during 72 h (rats) and 96 h (dogs) were 74% and 19%, 66% and 25%, respectively. The radioactivity excreted in the bile was 34% during 48 h and was followed by partial reabsorption from the gastrointestinal tract. 4. High radioactivities were observed in the digestive organs, mesenteric lymphnodes, liver, pancreas, urinary bladder, fat tissue, kidney and spleen after oral administration to rats.
（±）-（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（苯磺酸氨氯地平，KW-3049）已被开发用作抗高血压和抗心绞痛药物。使用Wistar大鼠和比格犬对14C标记的KW-3049进行单次口服给药后，研究了其吸收、分布和排泄情况。结果总结如下：1. 给大鼠口服14C-KW-3049后，血浆放射性在0.5小时达到最大值，在4小时出现第二个峰值，并呈双相下降，生物半衰期约为6小时和38小时。2. 给犬口服14C-KW-3049后，血浆放射性在1小时达到最大值，并呈双相下降，生物半衰期约为2小时和25小时。3. 给大鼠和犬口服后，72小时（大鼠）和96小时（犬）内粪便和尿液中放射性的排泄量分别为74%和19%、66%和25%。48小时内胆汁中排泄的放射性为34%，随后部分从胃肠道重吸收。4. 给大鼠口服后，在消化器官、肠系膜淋巴结、肝脏、胰腺、膀胱、脂肪组织、肾脏和脾脏中观察到高放射性。
