Involvement of intestinal permeability in the oral absorption of clarithromycin and telithromycin

Biopharm Drug Dispos. 2014 Sep;35(6):321-9. doi: 10.1002/bdd.1900. Epub 2014 Jun 27.


The involvement of intestinal permeability in the oral absorption of clarithromycin (CAM), a macrolide antibiotic, and telithromycin (TEL), a ketolide antibiotic, in the presence of efflux transporters was examined. In order independently to examine the intestinal and hepatic availability, CAM and TEL (10 mg/kg) were administered orally, intraportally and intravenously to rats. The intestinal and hepatic availability was calculated from the area under the plasma concentration-time curve (AUC) after administration of CAM and TEL via different routes. The intestinal availabilities of CAM and TEL were lower than their hepatic availabilities. The intestinal availability after oral administration of CAM and TEL increased by 1.3- and 1.6-fold, respectively, after concomitant oral administration of verapamil as a P-glycoprotein (P-gp) inhibitor. Further, an in vitro transport experiment was performed using Caco-2 cell monolayers as a model of intestinal epithelial cells. The apical-to-basolateral transport of CAM and TEL through the Caco-2 cell monolayers was lower than their basolateral-to-apical transport. Verapamil and bromosulfophthalein as a multidrug resistance-associated proteins (MRPs) inhibitor significantly increased the apical-to-basolateral transport of CAM and TEL. Thus, the results suggest that oral absorption of CAM and TEL is dependent on intestinal permeability that may be limited by P-gp and MRPs on the intestinal epithelial cells.

Keywords: Caco-2 cell monolayers; clarithromycin; intraportal administration; oral bioavailability; telithromycin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B / metabolism
  • Administration, Oral
  • Animals
  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / blood
  • Anti-Bacterial Agents / pharmacokinetics*
  • Biological Availability
  • Caco-2 Cells
  • Clarithromycin / administration & dosage
  • Clarithromycin / blood
  • Clarithromycin / pharmacokinetics*
  • Humans
  • Intestinal Absorption*
  • Intestinal Mucosa / metabolism*
  • Ketolides / administration & dosage
  • Ketolides / blood
  • Ketolides / pharmacokinetics*
  • Liver / metabolism
  • Male
  • Multidrug Resistance-Associated Proteins / metabolism
  • Permeability
  • Rats, Wistar


  • ATP Binding Cassette Transporter, Subfamily B
  • Anti-Bacterial Agents
  • Ketolides
  • Multidrug Resistance-Associated Proteins
  • Clarithromycin
  • telithromycin