Lack of Pharmacokinetic Interaction between Linezolid and Antacid in Healthy Volunteers

Abstract

Several antibiotics show significant pharmacokinetic interactions when they are given orally concomitantly with antacids. The objective of this study was to evaluate the effects of antacid (containing magnesium) on the pharmacokinetics of linezolid. A single dose of 600 mg linezolid was given orally alone and 10 min after administration of the antacid Maalox 70mVal, which contains 600 mg magnesium hydroxide and 900 mg aluminum hydroxide, to nine healthy males and nine healthy females in a crossover and randomized study. Linezolid plasma concentrations were determined by high-performance liquid chromatography, and pharmacokinetic parameters were calculated for both treatments. Coadministration with antacids did not change the pharmacokinetics of linezolid. The ratios (90% confidence intervals) of the individual values of the area under the concentration-time curve and the maximum concentration in plasma (C(max)) (linezolid plus antacid versus linezolid alone) were 1.01 (0.99 to 1.02) and 0.99 (0.96 to 1.02), respectively. Likewise, no significant difference in any of the other pharmacokinetic parameters was observed between the treatment groups (the time to C(max), lag time, volume of distribution [V/F], and clearance [CL/F]). However, a significant sex difference was observed for AUC, C(max), V/F, and CL/F; and these differences could be almost completely explained by the differences in body weight between males and females. No clinically relevant adverse effects were detected under either condition. The coadministration of antacids had no effect on the pharmacokinetics of linezolid. This demonstrates that the oral absorption of linezolid was not affected by the presence of antacids containing magnesium hydroxide and aluminum hydroxide. Antacids can be safely administered together with linezolid.