Nonlinear absorption of methylprednisolone by absorptive and secretory transporters

作者：Tomita Mikio^*; Watanabe Atsuko; Fujinaga Ikue; Yamakawa Tomoko; Hayashi Masahiro

来源：International Journal of Pharmaceutics, 2010, 387(1-2): 1-6.

DOI：10.1016/j.ijpharm.2009.10.042

• Methylprednisolone
• Nonlinear absorption
• Rat intestine
• Caco-2 cell monolayers

The intestinal absorption rate constant of methylprednisolone (MP) evaluated by the loop method increased significantly with increasingly higher concentrations of the drug up to 500 mu M in a nonlinear fashion but did not increase further at higher concentrations. Mucosal-to-serosal directed permeation of MP across rat jejunal sheets also increased in a nonlinear fashion in a low concentration range (100-150 mu M), followed by a decrease as the concentration increased further. whereas serosal-to-mucosal directed permeation decreased in a concentration-dependent manner. Vectorial transport of MP across Caco-2 cell monolayers was observed, with greater transport in the basolateral-to-apical direction at 37 degrees C. These observations suggest that MP is taken up in the intestinal epithelial cells by a carrier-mediated transport mechanism. The absorptive and secretory clearance of MP increased and decreased with P-glycoprotein (P-gp) inhibitors, respectively. These results strongly suggest that MP is secreted into the intestinal lumen predominantly by P-gp. We conclude that intestinal transport of MP involves P-gp or some other transporters in both the absorptive and secretory directions, and complex nonlinear intestinal absorption characteristics can be ascribed to the existence of multiple transport mechanisms.

• 出版日期2010-3-15