NORMOCALCEMIC EFFECT OF GALLIUM NITRATE IN A HYPERCALCEMIC RAT MODEL

An established rat hypercalcemia model was used to study the effects o f gallium nitrate on elevated serum calcium levels. Gallium nitrate wa s administered by i.v. or i.p. injection at daily doses of 0.07-0.45 m mol/kg for 5 days to the hypercalcemic rats beginning 1 day following surgery. A dose-correlated normocalcemic response was observed. Galliu m nitrate administered late after the induction of the hypercalcemic s tate was also effective in reducing serum calcium levels. The p.o. adm inistrations, 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 co ncentration versus time curve (0-24 h) of gallium in normal rats were comparable after i.v. [49.2 (pg/ml)h] or i.p. [57.0 (mu g/ml)h] inject ions. In contrast, the p.o. route achieved only 15% bioavailability, w hich may explain the ineffectiveness of p.o. administered gallium nitr ate at that dose level. This study suggests that daily i.v. bolus inje ctions of gallium nitrate for managing hypercalcemia may be potentiall y as effective as the current regimen of continuous i.v. infusion.