Reduction in absorption of gallium maltolate in adult horses following oral administration with food: chemistry and pharmacokinetics

Gallium ( G a) is under study for the treatment of osteolytic disorders in equines. Previous studies indicate that oral gallium maltolate ( G a M ) would provide a higher bioavailability than oral G a salts. However, oral administration to adult horses of 2 mg/kg of G a M , in the form of a solution mixed with food, did not lead to detectable Ga levels in plasma. Therefore, a study was performed to model the chemical behaviour of G a M in the digestive tract. The equilibrium formation constants for G a(III) and maltol were calculated by means of UV –visible measurements and validated by 1 H ‐ NMR measurements at selected p H values. Data indicate that the dissociation of G a M in aqueous solutions is very rapid, while the re‐association is slower. Based on these results, poor G a absorption seems to be due to the equilibrium dissociation of G a M in the stomach and to its slow formation rate in the intestine. The concomitant presence of high concentrations of phytates (strong charged metal chelating agents, which represent about 1% of dry matter in vegetables) might also explain the low absorption of G a M by the gastrointestinal tract. Methods of optimizing G a absorption after oral administration of G a M require further investigation.