EFFECT OF AN ANTACID CONTAINING MAGNESIUM AND ALUMINUM ON ABSORPTION,METABOLISM, AND MECHANISM OF RENAL ELIMINATION OF PEFLOXACIN IN HUMANS

The effects of an antacid containing magnesium and aluminum hydroxide on the pharmacokinetics of pefloxacin in 10 healthy volunteers were in vestigated. In a randomized crossover design, each subject received an oral dose of 400 mg of pefloxacin either with or without multiple dos es of the antacid. The concentrations of pefloxacin and its metabolite s in plasma and urine were determined by high-performance liquid chrom atography assays. We found that coadministration of magnesium and alum inum hydroxide caused a decrease of levels of pefloxacin in plasma and urine. The area under the plasma concentration-time curve decreased s ignificantly (P < 0.001), suggesting impaired absorption of pefloxacin from the gastrointestinal tract. The relative bioavailability of pefl oxacin after the antacid treatment was 44.4% +/- 23.8%, compared with that after a single administration. The underlying mechanism of this d rug interaction is the formation of chelate complexes and probably als o physical adsorption to the aluminum hydroxide gel. The metabolism of pefloxacin was not altered by the antacid treatment. Renal clearance was found to depend on urinary pH. Terminal half-life was significantl y shorter after the antacid treatment, probably because of an increase in nonrenal clearance. In conclusion, pefloxacin should be given at l east 2 h before the antacid to ensure sufficient therapeutic efficacy of the quinolone.