Purpose] Macrolide and ketolide antibiotics are orally administered for treatment of infections. However, the intestinal absorption mechanisms of these antibiotics are not well known. In this study, we studied the intestinal absorption mechanisms of clarithromycin (CAM) as a macrolide and telithromycin (TEL) as a ketolide antibiotic. [Methods] In vivo animal study: CAM and TEL were intravenously or orally administrated to rats and the bioavailability was calculated. In vitro transport study:

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... and TEL were applied to apical side or basolateral side of Caco-2 cell monolayers. After incubation, the amount of CAM and TEL permeated were determined. The effects of verapamil as a MDR1 substrate on the permeation of CAM and TEL were evaluated. Also, the effects of CAM and TEL on the permeation of rhodamine123 as a MDR1 substrate were evaluated. ATPase activity assay: CAM and TEL-stimulated MDR1 ATPase activity was evaluated by Human MDR1 Membranes (GenoMembrane). [Results and Discussion] In vivo animal study, the bioavailability of CAM and TEL was 45% and 28%, respectively. In vitro transport study, the apical to basolateral transport of CAM and TEL were significantly lower than the basolateral to apical transport. Verapamil significantly increased the apical to basolateral transport of CAM and TEL. CAM and TEL significantly increased the apical to basolateral transport of rhodamine123. In the ATPase activity assay, CAM and TEL stimulated the MDR1 ATPase activity. These results suggest that MDR1 associates with the intestinal absorption of CAM and TEL. [Conclusions] This study suggests that low bioavailability of CAM and TEL is based on MDR1-mediated intestinal transport characteristics.