Studies on the Mechanism of Pharmacokinetic Interaction of Aluminum hydroxide, an Antacid, with New Quinolones in Rats

The studies on the mechanism of pharmacokinetic interaction of aluminum hydroxide with new quinolones, ofloxacin, enoxacin and norfloxacin, were performed in rats. New quinolones (20 mg/kg) were administered orally with or without aluminum hydroxide or aluminum chloride (50 mg/kg). Co-administration of aluminum hydroxide induced a significant decrease in Cmax of enoxacin and norfloxacin, and in the AUC values of the three drugs. This effect was enhanced by co-administration of aluminum chloride. The combination of aluminum hydroxide caused a significant increase in the intestinal contents and decrease in urinary excretion of new quinolones. The formation of the stable chelate of new quinolones with Al3+ ions formed from aluminum hydroxide in the same acidic solution as gastric juice was observed. Thus, it is concluded that the co-administration of aluminum hydroxide affects the pharmacokinetics of new quinolones, probably, by the inhibition of the intestinal absorption of new quinolones by the chelate formation of these compounds with Al3+ ions released from aluminum hydroxide in the gastric juice.