The effect of milk on plasmatic and tissue levels of macrolides: in vivo study in rats

Abstract

The ingestion of milk with drugs, particularly some antibiotics, is frequently recommended in order to decrease possible gastrointestinal discomfort. The objective of this study was to assess the interference of milk in the absorption and tissue levels of macrolide antibiotics (erythromycin, clarithromycin, roxithromycin and azithromycin). Forty female rats received surgicallyimplanted PVC sponges on their backs. One week later, granulomatous tissue was observed and the animals were divided into eight groups, which received erythromycin, clarithromycin, roxithromycin and azithromycin with and without milk. One hour after administration of antibiotic, the animals were sacrificed. The serum and tissue samples were submitted to microbiological assay with Micrococcus luteus ATCC 9341, in order to determine drug concentration. Milk did not cause any reduction in the serum and tissue levels of azithromycin and clarithromycin (p>0.05, t-test). However, ingestion of milk reduced by approximately 28.7% the roxithromycin (p<0.0001, t-test) and by 34.1% the erythromycin (p<0.0001, t test) serum concentrations. Similar effects were observed on tissue levels. Milk ingestion caused a reduction of approximately 20.8% in the roxithromycin (p<0.0001, t-test) and 40% in the erythromycin (p<0.0001, t-test) tissue levels. We concluded that erythromycin and roxithromycin should be not administered with milk.