Effect of an aluminum- and magnesium-containing antacid on the bioavailability of garenoxacin in healthy volunteers.

Study Objective: To evaluate the effect of an aluminum- and magnesium-containing antacid (Al-Mg antacid), which contains a high concentration of cations, on the pharmacokinetics of garenoxacin.

Design: Prospective, randomized, open-label, control-balanced, residual-effects-design study.

Setting: Pharmaceutical company-affiliated study clinic.

Subjects: Twenty healthy volunteers who were garenoxacin naïve.

Intervention: Subjects were randomly assigned to receive three of six oral treatments, each separated by a 7-day washout period: garenoxacin 600 mg administered alone, with concomitant Al-Mg antacid, 2 or 4 hours before Al-Mg antacid, or 2 or 4 hours after Al-Mg antacid. The Al-Mg antacid dose was 20 ml, which contained aluminum hydroxide 900 mg and magnesium hydroxide 800 mg.

Measurements And Main Results: The pharmacokinetics and safety of garenoxacin were assessed. For each treatment, serial blood samples for pharmacokinetic analysis of garenoxacin were collected before and up to 72 hours after garenoxacin dosing. Absence of effect of Al-Mg antacid on garenoxacin area under the concentration-time curve from time zero extrapolated to infinity (AUC(0-infinity)) and maximum observed plasma concentration (C(max)) were concluded if the 90% confidence interval of the adjusted geometric mean ratios with and without the antacid were contained within 0.80-1.25 and 0.70-1.43, respectively. Exposure to garenoxacin measured by AUC(0-infinity), a parameter well correlated with efficacy, was reduced by 58% when coadministered with Al-Mg antacid and reduced by 22% and 16% when administered 2 and 4 hours after the antacid, respectively. Administration of garenoxacin 4 hours before Al-Mg antacid had no effect on AUC(0-infinity) or C(max) of garenoxacin, whereas administration 2 hours before the antacid resulted in a nonclinically relevant (12%) reduction in AUC(0-infinity) of garenoxacin.

Conclusion: Exposure to garenoxacin was significantly decreased when garenoxacin was coadministered with Al-Mg antacid or within 2 hours after the antacid. The magnitude of the changes in garenoxacin exposure suggests that garenoxacin should be administered at least 2 hours before or 4 hours after administration of Al-Mg antacid or other cation-containing products.