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There is an increasing interest in improving treatment of liver diseases. Normal drug administration by intravenous and oral route have difficulty in achieving a local site of action in the liver. Although the direct way of application to the liver surface should yield local drug distribution, the drug absorption from the liver surface has not been reported in literature. In the present study, we have analyzed the absorption mechanism of organic anions as a model after application to the rat liver surface in vivo employing a cylindrical glass cell. Every drug appeared gradually in the plasma, followed by excretion into the bile. This indicates the possibility of drug absorption from the liver surface. The pharmacokinetics of phenol red, of which absorption rate was fastest, after application to the rat liver surface was explained by the model incorporating the first-order absorption. Because the effect of dose and transport inhibitors on the absorption of phenol red could not be recognized, a specific transport system might not be involved in the process of absorption from the liver surface. Moreover, protein binding tended to suppress the absorption of organic anions, and molecular weight was found to be a determinant factor of absorption from the liver surface, by utilizing dextrans with different molecular weights. Also, the targeting efficacy to the liver was enhanced by application to the liver surface, as high liver/plasma concentration ratio as compared with i.v. administration. Furthermore, we confirmed that the change of the drug absorption behavior from the liver surface in the basic diseased state (CCl4- or D-galactosamine-treated rat) was not significant. Consequently, the present results on the mechanism of drug absorption from the liver surface provide an useful information in the development of new administration route for drug delivery to the target site in liver.

STUDY ON THE DRUG ABSORPTION MECHANISM FROM THE LIVER SURFACE: ITS APPLICATION TO DRUG TARGETING TO THE LIVER