EFFECT OF APPLICATION VOLUME AND AREA ON THE ABSORPTION OF PHENOL RED, AS A MODEL-DRUG, FROM THE LIVER SURFACE IN RATS

To determine the influence of the method of administration of a pharma ceutical formulation we have examined the importance of application vo lume and area in the absorption of phenol red, as a model drug, from t he rat-liver surface. When 1 mg phenol red was applied to the rat-live r surface, in-vivo, in three volumes (0.1, 0.2 or 0.334 mL) using a cy lindrical glass cell (i.d. 9 mm), the shape of the plasma concentratio n profile differed greatly, particularly the maximum concentration. Th ese patterns were well fitted by a two-compartment model with first-or der absorption, and the absorption-rate constant K-a obtained was inve rsely proportional to the application volume. The absorption ratio and biliary recovery of phenol red after 6 h increased with glass cell ar ea (i.d. 6, 9 or 14 mm; area 0.28, 0.64 or 1.54 cm(2)). Furthermore, t he permeability coefficient P-app derived from K-a did not depend on a pplication area, indicating no difference in the absorption characteri stics of the liver surface. This also implies transport of the drug by passive diffusion from the liver surface. After intraperitoneal admin istration to the rat-liver surface for clinical application, increasin g the application volume resulted in the delayed disappearance of phen ol red from the plasma. However, the difference was not as marked as t hat obtained by use of the glass cell. The assumption that the effecti ve area relating to the absorption changed with the application volume enabled us to estimate P-app. Consequently, we speculate that absorba bility can be estimated precisely by consideration of application volu me and area.