Oral absorption and pharmacokinetics of rebamipide and rebamipide lysinate in rats.
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.
Shin
Beom Soo
BS
College of Pharmacy, Sungkyunkwan University, Suwon, Kyeonggi-do, Korea.
Kim
Chul Hwan
CH
Jun
Yoon Sik
YS
Yoon
Chi Ho
CH
Rho
Jae Il
JI
Lee
Kang Choon
KC
Han
Hye Seon
HS
Yoo
Sun Dong
SD
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
D000897:Anti-Ulcer Agents; D015363:Quinolones; D014867:Water; C052785:rebamipide; D000409:Alanine