Bioavailability of Clarithromycin Cyclodextrin Ternary Complexes Upon Oral Administration to Healthy Beagle Dogs

Abstract

The dissolution profiles of clarithromycin (CLM) and its β-cyclodextrin–citric acid ternary complexes (CTC) were examined. CTC showed an enhanced dissolution rate in pH 6.8 phosphate buffers. The relative bioavailability was evaluated by comparing area under the plasma concentration–time curve (AUC) of the pure CLM with that of its cyclodextrin–citric acid ternary complexes those were filled into hard gelatin capsules. To compare the pharmacokinetic behavior, both plasma levels of parent compound and the active metabolite 14-OH-CLM concentrations were estimated. The relative bioavailability value as the ratios of CLM of mean total AUC for CTC relative to CLM was 120.3%. The relative bioavailability value as the ratios of 14-OH CLM of mean total AUC for CTC relative to CLM was 95.3%. The results suggest that the absorption of CTC in beagle dogs was slightly improved because of the enhanced dissolution rate of CTC at pH 6.8.

Keywords:

• clarithromycin
• ternary inclusion complexes
• bioavailability

ACKNOWLEDGMENTS

This work was financially supported by the 863 Program of China (Grant No. 2003AA2Z347C). We also thank Mr. Si-wei Chen for assistance in this experiment.