Effect of application volume and area on the absorption of phenol red as a model drug from the liver surface in rats

We examined the importance of application volume and area in the absorption of phenol red as a model drug from the rat liver surface, for pharmaceutical formulation concerning administration form. When 1 mg of phenol red was applied to the rat liver surface in-vivo using a cylindrical glass cell (i.d. 9 mm) in three volumes (0.1, 0.2 or 0.334 mL), the shape of the plasma concentration pattern differed greatly, particularly the maximum concentration. These patterns were well fitted by a two-compartment model with first-order absorption, and the obtained absorption rate constant Ka decreased inversely according to the application volume. The absorption ratio and biliary recovery of phenol red at 6 h was increased with glass cell area (i.d. 6, 9 or 14 mm; area 0.28, 0.64 or 1.54 cm2). Furthermore, the permeability coefficient Papp derived from Ka did not depend on application area, indicating no difference in absorption characteristics of liver surface. This also implies transport of a drug by a passive diffusion from the liver surface. After intraperitoneal administration to the rat liver surface for clinical application, increase in application volume resulted in the delayed disappearance of phenol red from plasma. However, the difference was not as marked as that using a glass cell. The assumption that the effective area relating to the absorption changed with the application volume enabled us to estimate Papp. Consequently, we speculate absorbability can be estimated precisely by considering application volume and area

Effect of viscous additives on drug absorption from the liver surface in rats using phenol red as a model

The purpose of this study is to obtain information that can be used to improve controlled release and residence time of drugs on the liver surface. Using carboxymethylcellulose sodium salt (CMC-Na) and polyvinyl alcohol (PVA), we examined the effect of viscous formulations on the absorption of phenol red as a model. In the presence of 3% CMC-Na or 15% PVA, the maximum plasma concentration of phenol red decreased after application to the rat liver surface using a cylindrical glass cell. The absorption ratios in 6 h calculated from the remaining amount of phenol red in the glass cell were 68.6, 60.5 and 48.7% (control: 73.1%) in the presence of 1 or 3% CMC-Na and 15% PVA, respectively. As a result of the reduction in the absorption ratio, the amount of phenol red excreted into the bile and urine in 6 h was decreased by the addition of the viscous additives. The decrease in absorption rate was characterized by a pharmacokinetic analysis of the plasma concentration profile. The change in absorption rate differed between the viscous additives, reflecting the result of the in vitro release experiment. Accordingly, the possibility that the drug absorption rate from the liver surface can be altered by viscous additives was suggested to have a promising prospect for therapeutic use