Oral Absorption and Pharmacokinetics of Rebamipide and Rebamipide Lysinate in Rats

Abstract

Rebamipide is an anti‐ulcer agent exhibiting a low aqueous solubility and a poor oral bioavailability. This study was conducted to examine if the rebamipide lysinate salt form would exhibit improved solubility profiles and higher oral bioavailability compared with rebamipide free acid. Both compounds showed pH‐dependent solubility profiles, with the solubility of rebamipide lysinate dramatically improved at a median pH of 5.1 (17‐fold increases) over free acid, but the improvement in the solubility was not as pronounced in artificial gastric and intestinal fluids (1.4‐ and 1.9‐fold increases, respectively). The Cl, Vss and t1/2 in rats after i.v. injection of rebamipide (0.5 mg/kg) averaged 21.0 ± 3.2 ml/min/kg, 0.3 ± 0.0 L/kg, and 0.4 ± 0.1 hr, respectively. No significant difference was observed in these parameters between rebamipide and rebamipide lysinate. Despite improved solubility profiles, the absolute oral bioavailability of rebamipide lysinate was not increased (5.1 vs. 4.8%) nor did AUC (407.8 vs. 383.6 ng.hr/ml) and Cmax (87.4 vs.77.0 ng/ml) compared with rebamipide free acid. Rebamipide lysinate, however, showed a more rapid absorption, and initial serum drug concentrations were higher than those found for rebamipide free acid.