Absorption, distribution and excretion of 14C-benidipine hydrochloride after repeated administration to rats.
The absorption, distribution and excretion of (+/-)-(R*)-2,6-dimethyl-4-(m-nitrophenyl)-1,4-dihydropyridine-3,5-dicarb oxylic acid (R*)-1-benzyl-3-piperidinyl ester, methyl ester hydrochloride (benidipine hydrochloride, KW-3049) were studied after repeated doses to rats. The results were summarized as follows: 1. After oral repeated administration once a day for 3 weeks, the radioactivities in blood and tissues increased up to the 14th day, and thereafter they tended to show the steady state. 2. The radioactivity in the tissues at 1 h after last dosing was compared with that at 1 h after single administration. Both tissue distribution patterns were not markedly different, but the concentrations in the liver, testicles, skin and descending aorta significantly increased, showing approximately the 2-fold radioactivities. 3. The radioactivities were excreted in the urine (6%) and feces (88%). The excretion of radioactivity in urine and feces did not change markedly during the repeated administration period.
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; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005243:Feces / Q000032:analysis; 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