Effect of an antacid containing magnesium and aluminum on absorption, metabolism, and mechanism of renal elimination of pefloxacin in humans

Abstract

The effects of an antacid containing magnesium and aluminum hydroxide on the pharmacokinetics of pefloxacin in 10 healthy volunteers were investigated. In a randomized crossover design, each subject received an oral dose of 400 mg of pefloxacin either with or without multiple doses of the antacid. The concentrations of pefloxacin and its metabolites in plasma and urine were determined by high-performance liquid chromatography assays. We found that coadministration of magnesium and aluminum hydroxide caused a decrease of levels of pefloxacin in plasma and urine. The area under the plasma concentration-time curve decreased significantly (P < 0.001), suggesting impaired absorption of pefloxacin from the gastrointestinal tract. The relative bioavailability of pefloxacin after the antacid treatment was 44.4% ± 23.8%, compared with that after a single administration. The underlying mechanism of this drug interaction is the formation of chelate complexes and probably also 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 significantly shorter after the antacid treatment, probably because of an increase in nonrenal clearance. In conclusion, pefloxacin should be given at least 2 h before the antacid to ensure sufficient therapeutic efficacy of the quinolone.Under clinical conditions, antacids may be administered together with the new quinolone antibacterial agents. Antacids are known to alter both absorption of drugs from the gastrointestinal tract and renal elimination (12). A decrease in the rate and extent of absorption of orally administered drugs by a concomitant antacid treatment may reduce drug activity considerably. Alteration of urinary pH may lead to changes in renal excretion of acidic and basic drugs.In this investigation, the influence of an antacid containing magnesium and aluminum hydroxide on the pharmacokinetics and bioavailability of pefloxacin was evaluated. Pefloxacin is a newer quinolone carboxylic acid derivative with a broad spectrum of activity (3). A decrease in the bioavailability of several quinolones after concomitant intake of magnesium-aluminum hydroxide has recently been described elsewhere (5, 9, 13, 18, 19) and reviewed (4, 24). However, the extent of this interaction among individual quinolones, was quite different, which makes a prediction of the extent of the effect of the antacid on new derivatives difficult. Therefore, antacid-quinolone interaction studies are required for each newly developed quinolone. Pefloxacin differs from other quinolones in its extensive metabolism and in its considerable reabsorption in the kidney tubules (14). For that reason, an interaction with antacids at the hepatic and renal sites was also assessed in this study.

Elimination of Fecal Enterobacteriaceae by Intravenous Ciprofloxacin Is not Inhibited by Concomitant Sucralfate - a Microbiological and Pharmacokinetic Study in Patients

“…Physical adsorption to aluminum hydroxide gel has been proposed as a second mechanism, which may affect hydrophilic fluoroquinolone derivatives such as ciprofloxacin, norfloxacin, and enoxacin in particular, while lipophilic compounds are less affected [43]. The interaction is further facilitated by the lack of a substituent at the 5-position of ciprofloxacin [44].…”

Interaction of pefloxacin and enoxacin with the human cytochrome P450 enzyme CYP1A2

“…Plasma samples were analyzed for caffeine, 18 unchanged pefloxacin, 19 and unchanged enoxacin 20 by reversed‐phase HPLC assays. Concentrations of metabolites of caffeine or of quinolones were not determined in the vivo studies.…”

Effect of metal ions on the in vitro availability of enoxacin, its in vivo implications, kinetic and antibacterial studies

“…This is because enoxacin ligand interacted with the metal ions possibly leading to the formation of drug metal chelates. 13 It was further observed that the ability of enoxacin to interact with metal ion was pH dependent and was greater in extreme pH conditions i.e. pH 1.5 and pH 9.…”