title: 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, V(ss) 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 x hr/ml) and C(max) (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.
authors.affiliation: College of Pharmacy, Sungkyunkwan University, Suwon, Kyeonggi-do, Korea.
authors.forename: Beom Soo
authors.initials: BS
authors.lastname: Shin
authors.forename: Chul Hwan
authors.initials: CH
authors.lastname: Kim
authors.forename: Yoon Sik
authors.initials: YS
authors.lastname: Jun
authors.forename: Chi Ho
authors.initials: CH
authors.lastname: Yoon
authors.forename: Jae Il
authors.initials: JI
authors.lastname: Rho
authors.forename: Kang Choon
authors.initials: KC
authors.lastname: Lee
authors.forename: Hye Seon
authors.initials: HS
authors.lastname: Han
authors.forename: Sun Dong
authors.initials: SD
authors.lastname: Yoo
mesh_terms: D000284:Administration, Oral; D000409:Alanine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics*; D000818:Animals; D000897:Anti-Ulcer Agents / Q000097:blood / Q000737:chemistry / Q000494:pharmacology; D019540:Area Under Curve; D001682:Biological Availability; D004353:Drug Evaluation, Preclinical / Q000379:methods; D006207:Half-Life; D006863:Hydrogen-Ion Concentration; D007275:Injections, Intravenous; D008297:Male; D015363:Quinolones / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility / Q000187:drug effects; D014867:Water
chemical_list: D000897:Anti-Ulcer Agents; D015363:Quinolones; D014867:Water; C052785:rebamipide; D000409:Alanine