Metabolic Fate of 4-amino-1-hydroxybutylidene-1, 1-bisphosphonatete(alendronate) (III): Plasma Concentration, Distribution in Bone and Excretion after Intravenous Administration to Beagle Dogs

Abstract

Plasma concentration, bone distribution, and excretion after single intravenous administration of [¹⁴C]-alendronate to beagle dogs were investigated.
1. The levels of plasma radioactivity after administration of 0.05 mg/kg of [¹⁴C]-alendronate to beagle dogs declined triphasically, and the half-life of each phase was 25 minutes, 1.6 and 12.2 hours, respectively.
2. The cumulative excretion rates of radioactivity within 168 hours after administration of [¹⁴C]-alendronate was 36% of dose in urine and 8% in feces. Radioactivity was mainly excreted in the urine as in the case of rats, and the excretion in urine was almost completed in 24 hours after administration.
3. The levels of radioactivity in bones at 168 hours after administration of 0.05 mg/kg of [¹⁴C]-alendronate was 248.9 to 391.7 ng eq./g in vertebra and long bones, and 40.0 ng eq./g in calvaria. The difference of the concentration among bones was observed as in the case of rats. The autoradiography of the long bones revealed the higher level of radioactivity in the epiphysis and metaphysis than that in the diaphysis. High levels of radioactivity were observed along the growth plate of the long bone. On the basis of these results, it is suggested that alendronate is distributed in bones, especially in the high turnover region.