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Normocalcemic Effect of Gallium Nitrate in a Hypercalcemic Rat Model¹

Department of Clinical Investigation, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030 [J-R. L., N. S. B., R. A. N., D. H. H.], and Fujisawa USA, Inc., Deerfield, Illinois 60015 [I. B., S. M., F. L.]

An established rat hypercalcemia model was used to study the effects of gallium nitrate on elevated serum calcium levels. Gallium nitrate was administered by i.v. or i.p. injection at daily doses of 0.07–0.45 mmol/kg for 5 days to the hypercalcemic rats beginning 1 day following surgery. A dose-correlated normocalcemic response was observed. Gallium nitrate administered late after the induction of the hypercalcemic state was also effective in reducing serum calcium levels. The p.o. administrations, however, even at doses as high as 0.45 mmol/kg, did not reduce serum calcium to normal levels. The values of area under the concentration versus time curve (0–24 h) of gallium in normal rats were comparable after i.v. [49.2 (µg/ml)h] or i.p. [57.0 (µg/ml)h] injections. In contrast, the p.o. route achieved only 15% bioavailability, which may explain the ineffectiveness of p.o. administered gallium nitrate at that dose level. This study suggests that daily i.v. bolus injections of gallium nitrate for managing hypercalcemia may be potentially as effective as the current regimen of continuous i.v. infusion.

¹ Supported in part by Fujisawa Pharmaceutical Co., Ltd., and National Cancer Institute Grant CA 16672.

² Present address: ImmunoPharmaceutics, Inc., 11011 Via Frontera, San Diego, CA 92127.

³ Present address: SuperGen, Inc., 116 Claridge Drive, Libertyville, IL 60048.

⁴ To whom requests for reprints should be addressed, at Box 52, Department of Clinical Investigation, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030.

Received 8/ 9/94. Accepted 11/10/94.