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Effect of pamidronate in a rat hypercalcemia model induced by cholecalciferol.

Pamidronate (disodium 3-amino-1-hydroxypropylidene-1,1-bisphosphonate pentahydrate, CGP 23339A, CAS 57248-88-1) has been show to provide a potent antihypercalcemic effect through the inhibition of calcium release from the bone. The time course study on the antihypercalcemic effect of pamidronate was performed using a rat hypercalcemia model induced by orally administered cholecalciferol. The onset of the antihypercalcemic effect was observed within 48 h after a single i.v. injection of pamidronate at 1 mg/kg and this effect was sustained for 19 days. The time course of the antihypercalcemic effect of pamidronate in combination with calcitonin was also examined in the same model. The onset of the antihypercalcemic effect was observed within 4 h after combination therapy with a single i.v. injection of pamidronate at 1 mg/kg and successive i.m. injections of calcitonin at 3.2 IU/kg and the effect was of sufficient duration. These results suggest that pamidronate has a pronounced effect in controlling hypercalcemia and provides a long-lasting effect by a single i.v. administration. Moreover, the use of pamidronate in combination with calcitonin may be useful when a quicker onset of action is required clinically.