Absorption, distribution and excretion after oral administration of 14C-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) 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.
Kobayashi
H
H
Pharmaceutical Research Laboratories, Kyowa Hakko Kogyo Co., Ltd., Shizuoka, Japan.
Ohishi
T
T
Nishiie
H
H
Kobayashi
S
S
Inoue
A
A
Oka
T
T
Nakamizo
N
N
D000284:Administration, Oral; D000818:Animals; D001345:Autoradiography; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000493:pharmacokinetics*; D055598:Chemical Phenomena; D002621:Chemistry; D004285:Dogs; D006207:Half-Life; D007408:Intestinal Absorption; D008297:Male; D009543:Nifedipine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D051381:Rats; D014018:Tissue Distribution
D002121:Calcium Channel Blockers; C050883:benidipine hydrochloride; D009543:Nifedipine