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.

Rebamipide attenuates pain severity and cartilage degeneration in a rat model of osteoarthritis by downregulating oxidative damage and catabolic activity in chondrocytes

“…The treatment of rebamipide was initiated on the day of MIA injection. The previous pharmacokinetics study showed that peak plasma concentration of rebamipide was observed around 1 h after oral administration 28 . After that, the serum concentration of the compound was decreased constantly.…”

Formulation and Characterization of Cubosomes Containing REB for Improvement of Oral Absorption of the Drug in Human Volunteers

“…There were many trials for improvement of REB oral bioavailability like formulation of REB solid dispersion which made an improvement of bioavailability 2.71 times higher than that of the reference product in the ulcer-induced rat model 4 . While in another experiment for preparation of REB lysinate salt no significant difference was observed in bioavailability between REB and REB lysinate 8 . Also there was a trial for formulation of REB nanosuspension, which showed a slight increase in the bioavailability of REB nanosuspension compared with Mucosta® tablet 14 .…”

“…Improvement of bioavailability of a hydrophobic drug like REB is a major challenge in drug development. Various techniques have been reported to be advantageous for improving solubility and oral bioavailability of REB such as formulation of nanocrystals 5 , solid dispersion 6 , and salt formation techniques 7,8 .…”

Role of estrogen in spermatogenesis in initial phase males of the three‐spot wrasse (Halichoeres trimaculatus): Effect of aromatase inhibitor on the testis

“…The appropriate choice of counterion to form the salt can result in enhanced solubility which may translate into superior bioavailability 11. However, the full solubility advantage to be gained by administering salt forms is not always realized 12. This is most likely due to reversion to a more stable solid form during dissolution depending on experimental versus in vivo solution conditions.…”

“…This is most likely due to reversion to a more stable solid form during dissolution depending on experimental versus in vivo solution conditions. A soluble salt form can revert to the sparingly soluble free acid, base, or less soluble salt form during the dissolution in vitro ,13 in vivo ,12 and during storage,14 eliminating the bioavailability advantage one hoped to gain. When this conversion occurs during dissolution, it is by means of solution‐mediated phase transformation, that is, transition from one solid state to another via solution.…”