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

Gallium (Ga) is under study for the treatment of osteolytic disorders in equines. Previous studies indicate that oral gallium maltolate (GaM) would provide a higher bioavailability than oral Ga salts. However, oral administration to adult horses of 2 mg/kg of GaM, 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 GaM in the digestive tract. The equilibrium formation constants for Ga(III) and maltol were calculated by means of UV\u2013visible measurements and validated by 1H-NMR measurements at selected pH values. Data indicate that the dissociation of GaM in aqueous solutions is very rapid, while the re-association is slower. Based on these results, poor Ga absorption seems to be due to the equilibrium dissociation of GaM 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 GaM by the gastrointestinal tract. Methods of optimizing Ga absorption after oral administration of GaM require further investigation