Absorption, distribution and excretion of 14C-benidipineHCl in rats.

Abstract

Absorption, distribution and excretion of 14C-benidipine · HCl(KW-3049) were studied in rats after a single oral (1.0mg/kg) or intravenous (0.1mg/kg) administration and after repeated oral dosing for 21 days (1mg/kg).And, plasma unchanged drug levels were determined after repeated oral dosing of KW-3049 (1mg/kg) for 21 days to rats.1. Plasma levels reached the maximum of 126.4ng equiv./ml (male) or 246.6ng equiv./ml (female) at 0.5hr after oral dosing and the elimination half-lives at the terminal phase were 20.3hr and 30.Ohr in male and female rats, respectively.2. The highest level of radioactivity was found in the liver at 0.1hr after intravenous dosing. The level of radioactivity in central nervous system was the lowest.3. Maximum levels in most tissues were reached at 0.5hr after oral dosing. The liver had the highest level of radioactivity except the gastro-intestinal tract. The central nervous system had the lowest level of radioactivity.4. After intravenous or oral dosing in male rats, 18 or 19% of the dose was excreted in the urine and 84 or 74% of the dose in the feces, respectively. After oral dosing in female rats, 24 and 72% of the dose was excreted in urine and feces, respectively.5. Biliary excretion of radioactivity was 34% within 48hr after oral dosing.6. In the case of the repeated oral dosing for 21 days of KW-3049, plasma level of unchanged drug showed no change. The level of radioactivity in plasma after repeated daily dosing of 14C-KW-3049 increased by repeated dosing untill 14th dosing. Its level after final dose was 1.3 times higher than that after a single dose. Some tissues showed two to three times higher levels of radioactivity after repeated dosing. Excretion of radioactivity into the urine and feces was almost constant during repeated administration, and was 6 and 88%, respectively.