Abstract: | The effect of combined treatment with local hyperthermia and i.v. infusion of 5-fluorouracil was studied in 39 Wistar rats with a transplanted adenocarcinoma inoculated in the liver. Ten to 13 days later the rats were divided into three groups. Group A1 was subjected to local microwave hyperthermia (42 degrees C) for 1 h. During the hyperthermia, an i.v. infusion of 5-FU (20 mg/kg body weight) was given. In group A2 5-FU was administered under normothermic conditions. Group A3 received saline infusion under normothermic conditions. The mortality after infusion of 5-fluorouracil and hyperthermia increased during the first week after treatment. In group A1, a significant growth retardation of liver tumor was registered seven days after treatment. This effect was not superior to that of hyperthermia alone as previously described for the same experimental model. Studies of 5-FU pharmacokinetics in plasma were performed in another 20 Wistar rats. Ten rats were given an i.v. infusion of 5-FU during local hyperthermia, while the other 10 were infused under normothermic conditions. Plasma concentration of 5-FU was determined by isotachophoretic separation. The hyperthermia caused a faster decline in serum concentration of 5-FU, probably because of accelerated catabolism of the drug. |