EVALUATION OF DRUG TARGETING ABILITY TO THE LOCAL ORGAN SITE BY A NEW ADMINISTRATION UTILIZING ABSORPTION FROM ORGAN SURFACE

Abstract

We have proposed the organ surface as a novel application site of drugs, and elucidated the absorption mechanism from the organ surface. In the present study, we examined the drug distribution after application to the rat liver and kidney surface and evaluated possibility of site-selective drug targeting to the organ. We selected phenol red (PR), FITC-dextran (FD-4, Mw 4, 400), and 5-FU as model drugs. The concentration of the model drugs at the administered site after application to the rat liver surface was significantly higher than those in the other two sites. In addition, the concentration of PR and 5-FU in the right kidney after application to the rat right kidney surface was high compared with that in the left kidney, although no significant difference was observed in FD-4. A similar tendency was observed in the urinary excretion rate. Moreover, selectivity advantage of the organ surface application was proven kinetically based on the physiological model. Consequently, drug application to the organ surface could improve availability in the desired site of a new drug such as genome medicine.