| Abstract: | This study investigated the effect of epinephrine (a vasoconstrictor) and hydralazine (a vasodilator) on the hepatic disposition of 5‐fluorouracil (5‐FU) after application to the surface of the liver in rats. Normal livers were compared with a Walker 256 carcinoma cell tumor model. A cylindrical diffusion cell was attached to the liver surface. 5‐Fluorouracil was added into the diffusion cell in combination with vasomodulators or after pretreatment with epinephrine. After selected treatment times, the 5‐FU concentrations were assayed at three sites in the excised livers. The 5‐FU concentration in the region under the cell attachment site (site 1) was significantly higher after concomitant application of 5‐FU and epinephrine, compared with 5‐FU alone, and increased in an epinephrine dose‐dependent manner. On the other hand, preferential distribution of 5‐FU at site 1 was not seen when applied in combination with hydralazine. After 10 min of epinephrine pretreatment, the concentration of 5‐FU at site 1 was approximately two times higher than that for the control. Furthermore, the 5‐FU concentration at site 1 of the tumor model was greatly increased compared with the normal liver. These results suggest that application of epinephrine to the liver surface might enhance the accumulation of 5‐FU at the desired target site. |
