Influence of oral co-administered metallic drugs on ofloxacin pharmacokinetics

Following recent concern over probable interactions between the 4-quinolones and metal ions, the effect of co-administered drugs--sodium bicarbonate, potassium citrate, ferrous sulphate, magnesium trisilicate, calcium carbonate and aluminium hydroxide--on the saliva and urine pharmacokinetics of ofloxacin in healthy human volunteers has been investigated. The Cmax and AUC0-9 in saliva were generally in the range 1.05-1.40 mg/L and 4.89-6.16 mg.h/L, respectively, and were unaffected (P less than 0.05) by the metallic drugs, except aluminium hydroxide which lowered these values. Again, only aluminium hydroxide modified the Ka of ofloxacin, resulting in a slower absorption rate. However, none of the metallic drugs altered the T1/2 beta of the 4-quinolone in saliva. In-vitro studies using simulated gastric fluid showed that ferrous sulphate, aluminium hydroxide and calcium carbonate reduced ofloxacin availability to 67.4%, 69.3% and 73.8%, respectively. This effect was ascribed to the formation of complexes between ofloxacin and the metal ions concerned. Substantial correlation between in-vitro and in-vivo availability data was demonstrated in all cases except for ofloxacin combinations with ferrous sulphate and calcium carbonate. In general, there was also good correlation between the saliva and urine data.