Absorption, Distribution, Excretion, and Sex Differences in the Disposition of the Antiosteolytic Agent, Alendronate after Oral Administration in Rats

Abstract

Plasma concentrations, distribution, and excretion of [¹⁴C]-alendronate (MK-217/GTH-42) were investigated after oral administration to male and female rats.
1. The urinary excretion of radioactivity within 168 hr was 0.46% after oral administration at the dose of 5 mg/kg to male rats. The remaining drug was recovered in the feces quantitatively.
2. The radioactivity levels in the bone, trachea, and kidney were 3 to 6 times higher than that in the plasma at 30 minutes after a single oral administration at 5 mg/kg to male and female rats. The levels in the bone and trachea showed a plateau at 4 hr and decreased very slowly thereafter. High radioactivity levels were detected in the gastro-intestinal tract, but this was probably due to unabsorbed drug. In the other organs and tissues, the radioactivity was similar to or less than that in the plasma and decreased to almost undetectable levels at 24 hr after dosing. Sex differences were not observed in the tissue distribution of [¹⁴C]-alendronate in the rats.
3. After multiple oral administration at 5 mg/kg once daily for 7 days to female rats, the radioactivity levels in the trachea and bone were markedly higher than those after a single dosing. In the other organs and tissues, the overall profile of drug disposition was similar to that after a single dose.
These data indicated that the oral absorption of alendronate was very low (approximately 1 %), and that the drug distributed and accumulated selectively in the target site, the bone tissue.