The in‐vivo absorption of phenol red, bromphenol blue and bromosulphonphthalein, as model drugs, was investigated after application to the rat gastric serosal surface using a cylindrical glass cell. Absorption ratios of model drugs were estimated to be greater than 37% in 4 h. Absorbed drugs appeared gradually in plasma and bile. Drug concentrations in the application site at 1 h were 16–660 times that in the non‐application site in the stomach. Drug application to gastric serosal surface was effective with good absorption and efficient delivery to a local site in the stomach.

We report a very promising approach for liver site-selective drug delivery through drug instillation on liver surface. Phenol red, which was selected as a model drug, was accumulated in the instillation site after instillation on the rat liver surface. The site-selective localization was enhanced by gradually and continuously instilling a small amount of drug solution on the liver surface.

Animal models prepared by treatment with toxic compounds such as a carbon tetrachloride have been used to examine drug disposition in hepatic diseases. However, it is possible that these compounds accumulate and cause damage to other organs as they are administered systemically. In this study, we used the liver surface application technique to deliver a toxic compound to the liver to prepare an appropriate animal model in which only the liver is significantly damaged. To restrict the absorption area in the liver, a cylindrical diffusion cell was attached to the liver surface of male Wistar rats. Twenty-four hours after direct addition of carbon tetrachloride to the diffusion cell, plasma levels of glutamic-oxaloacetic transaminase (GOT) and glutamic-pyruvic transaminase (GPT), and hepatic malondialdehyde (MDA) concentration were increased, while there were no changes in plasma creatinine or renal MDA level. On the other hand, not only GOT, GPT and hepatic MDA, but also creatinine and renal MDA levels were markedly increased by p.o. and i.p. administration of carbon tetrachloride, suggesting renal damage. These results indicated that the animal models of liver damage prepared by utilizing drug delivery techniques to accumulate toxic compounds in the liver would enable us to investigate the precise effects of hepatic disorder on drug disposition.

The in‐vivo absorption characteristics of phenol red were studied after application to the rat gastric serosal surface, using a cylindrical glass cell. There was no significant difference between absorption ratios of 0.3, 1 and 3 mg phenol red in 6 h, suggesting linear absorption from the gastric serosal surface. When phenol red and bovine serum albumin were applied, drug absorption decreased with increasing protein concentration, indicating that protein binding is an important factor controlling drug absorption from the gastric serosal surface. These findings may be useful in the development of novel administration routes for drug delivery to the stomach.

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