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.