D-glucose elicits significant increase in the oral bioavailability of model BCS class III drugs in the rabbit

Abstract

BCS class III drugs suffer from limited intestinal absorption due to high hydrophilicity and low intestinal permeability. This research was undertaken in order to examine the effect of enhancing the net water influx in the gastrointestinal tract on the oral absorption of ranitidine HCl, atenolol, and acyclovir sodium as model BCS class III drugs using 2-way parallel pharmacokinetic study in the rabbit. The in vivo study involved oral administration of each drug in a hypo-osmolar aqueous solution as a control group. The second group (test group) involved administration of the same drugs in a hypo-osmolar solution containing 80 mM d-glucose and 30 mM NaCl. Serial plasma samples were obtained from the marginal ear vein at predetermined time intervals after drug administration. The AUC and Cmax of the three drugs were increased significantly in the presence of d-glucose. This increase was associated with significant delay in the Tmax. The results indicated that the oral bioavailability of ranitidine HCl, atenolol, and acyclovir sodium had been significantly enhanced in the presence of d-glucose. Thus, d-glucose coadministration can be used as a new approach to increase the intestinal permeability of BCS class III drugs.