A One Year Follow‐Up Study of the Distribution of 14C‐Clodronate in Mice and Rats

Abstract

The distribution of 14C-clodronate (dichloromethylene bisphosphonate) was studied in mice and rats by whole-body autoradiography and by measuring the 14C-activities in various tissues up to one year after a single intravenous dose. The results indicate that the deposition of clodronate in bone tissue of mice and rats is extremely strong and long lasting; in both animals, high radioactivities were measured even 12 months after the administration. In spleen, thymus, and small intestine of mice, 14C-activity could be detected 12 months after dosing. Small amounts of radioactivity were also detected in spleen of rats for 12 months, although much less than in spleen in mice. The results suggest that clodronate accumulates to some extent in the reticuloendothelial system of animals. They suggest further that the animal species should be carefully considered when interpreting the distribution kinetics of bisphosphonates, especially their accumulation in the reticuloendothelial system.