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We examined the effect of dose and transport inhibitors on the pharmacokinetics of phenol red as a model drug after application to rat liver surface in-vivo, employing a cylindrical glass cell (i.d. 9 mm, area 0.64 cm2), to elucidate the mechanism for drug absorption from liver surface membrane. Absorption ratios of phenol red in 6 h were determined to be 91.1, 91.8 and 89.9 % at a dose of 0.3, 1 and 3 mg, respectively. Also, the AUC value for plasma concentration profile of phenol red was proportional to the dose. It is thus suggested that absorption process of phenol red from rat liver surface does not approach saturability. Time course of remaining amount of phenol red in glass cell obeyed the first-order kinetics at 1 a dose of 0.3 mg, and its rate constant Ka was calculated to be 0.0069 min-1. Moreover, no significant difference was seen in Ka value within the dose range of 0.3 3 mg, which was estimated by curve fitting of the plasma concentration profile of phenol red after application to rat liver surface in the two-compartment model with first-order absorption. 2,4-Dinitrophenol (0.3 mg) and probenecid (0.5 and 1 mg), inhibitors of metabolic energy and anion transport respectively, had no significant effect on the pharmacokinetics of phenol red after application to rat liver surface. These data demonstrate that specific transport mechanism such as active transport is not involved in phenol red absorption from rat liver surface membrane. Introduction Liver site-specific drug delivery is of interest since normal treatment of liver diseases by intravenous and oral administration route has been frustrated by inadequate delivery into liver as well as toxicity in other organs. The direct way such as drug application to liver surface is supposed to be a useful method for drug delivery to the target site in liver. In our previous paper (Nishida et al 1994), we selected organic anions (phenol red, bromphenol blue and bromosulphonphthalein) as model drugs and examined their in-vivo behaviour after application to rat liver surface. Absorption ratios in 6 h of model drugs were relatively large (> 59 %) and significant prolongation of blood concentration was observed. For therapeutic application to liver disease, further work is required to elucidate the mechanism for drug absorption from liver surface membrane. The main purpose of present study is to obtain the information concerning the absorption mechanism from liver surface membrane. We selected phenol red as a model drug, of which absorption ratio was the largest among three organic anions. First, we