Absorption, Distribution and Excretion of SM-5600 in Mice, Rats and Dogs

The absorption, distribution and excretion of ethan-l-hydroxy-1, 1-diphosphonate (EHDP, SM-5600) were investigated in mice, rats and dogs after single oral or intravenous administration of 14C-SM-5600.1. When 14C-SM-5600 was orally administered (50 mg/kg), the absorption from gastro-intestinal tract was very low. In each animal species, 8-16 % of radioactivity was excreted in urine and 82-88 % in feces during 48 hr period after administration. Only a trace amount of radioactivity (0.2 %) was excreted in bile of rats.2. Serum levels reached maxima (Cmax) at 0.5 hr in mice and rats and at 2 hr in dogs. The Cmax levels were 7.5, 7.3 and 26.0 μgeq/ml in mice, rats and dogs, respectively.3. High levels of radioactivity were detected in bones in all animal species, but in other tissues the levels were rather low and rapidly decreasing.4. There were no sex-related-differences in the disposition of SM-5600 in rats.5. A dose dependency of absorption (Cmax and AUC) was observed in rats given lower doses than 50 mg/kg of 14C-SM-5600.