The effects of thionapthene-2-carboxylic acid-lysine on the hypercalcemia of malignancy in the rat.

Thionapthene-2-carboxylic acid (TNCA) was previously shown to lower serum calcium concentrations in hypercalcemic rats: however, oral administration of TNCA may cause gastric irritation. We have assessed thionapthene-2-carboxylic acid lysine salt (TNLY) for its effects on serum calcium concentration and survival in rats bearing the hypercalcemic Leydig cell tumor. TNLY (0.6-1.8 mmol/kg/day) produced a marked and prolonged dose-related decrease in serum calcium concentration. At the highest dose of 1.8 mmol/kg/day, hypocalcemia occurred. Effects were sustained for 96 hours or longer. In tumor-bearing rats that were not yet hypercalcemic, pretreatment with TNLY (0.9 mmol/kg/day) did not induce hypocalcemia and the onset of hypercalcemia was prevented. Neither TNLY nor dichloromethylene diphosphonate (CL2MDP), a potent inhibitor of bone resorption, significantly prolonged overall survival. We concluded that TNLY is a potent antihypercalcemic agent that warrants further testing for use in the treatment of hypercalcemic disorders.