Effect of Labrasol on the Permeabilities of Rhodamine 123, a P-gp Substrate Across the Rat Intestinal Membranes in vitro

OBJECTIVE To investigate the modulation of labrasol on the permeability characteristics of rhodamine123 (R123) across the intestinal membranes. METHODS The permeability (Papp) of R123 or fluorescein sodium (CF) via rat intestinal membranes at concentration of 5 μg·mL-1 was evaluated by an in vitro diffusion chamber system after the membranes were isolated from the intestine of rat, with or without the co-administration of labrasol at different low concentrations. And the concentration of R123 or CF in the receptor was determined by the fluorospectrophotometry. RESULTS There exists regional difference for the permeability of R123 across the rat intestinal membranes, which means the permeabilities of R123 was gradually decreased from jejunum, then ileum to colon. On the other hand, the serosal-to-mucosal transport (S-M) of R123 was much greater than its mucosal-to-serosal (M-S) transport. With co-administration of labrasol at low concentrations, the absorptive directed transport of R123 was significantly increased while its secretory directed transport was decreased, and the concentration-dependent effect was also found. However, no action of labrasol at test concentration was found on the transport of CF across the intestinal membranes. CONCLUSION It may be possible to improve the absorption of P-gp mediated drugs by co-administration of labrasol at low concentration, therefore to improve the oral bioavailability of these drugs.