PHARMACOKINETIC INTERACTIONS OF NORFLOXACIN WITH SOME METALLIC MEDICINAL AGENTS

The influence of some metallic therapeutic compounds on the pharmacokinetics of orally administered norfloxacin in healthy human volunteers has been examined. The in vitro availability of norfloxacin in dissolution media containing these metallic compounds was also studied. Peak saliva concentration (C(max)) and bioavailability (AUC0-9) of norfloxacin were reduced by approx. 35-fold, 3-5 fold and 40-50% when co-administered with ferrous sulphate, magnesium trisilicate and potassium citrate, respectively. Concomitant administration with sodium bicarbonate and aluminium hydroxide did not significantly modify the pharmacokinetics of norfloxacin but calcium carbonate reduced its bioavailability by 47%. The absorption and elimination rates of norfloxacin were not affected by the metallic compounds, except potassium citrate which decreased both the absorption and elimination of the drug. There was some degree of correlation between the saliva, urine and in vitro results. Based on the data obtained, it was evident that norfloxacin formed unabsorbable and/or antibacterially inactive/less active complexes with Fe2+, Mg2+ and Al3+. Complex formation, adsorption and pH-mediated effects were proposed as factors responsible for the alteration of the pharmacokinetics of norfloxacin by the co-administered agents. There was no clearly discernible link between the valency of the metal ion and its influence on norfloxacin pharmacokinetics.