Analysis and Distribution of Etoposide in Rat Brain Tumor Model: Intracarotid Versus Intracarotid with Angiotensin II—Induced Hypertension

The brain tissue distribution of etoposide has been investigated in 9L gliosarcoma-bearing rats with or without hypertension induced by angiotensin II (AT II). The rat brain tumor models were divided into the following two groups according to etoposide administration route: intracarotid injection (IC) group and intracarotid injection with hypertension induced by AT II (IHIC) group. Ten mg/kg of etoposide was given, and 30 min and 2, 4, 8, and 24 hr later the rats were sacrificed. The drug concentrations in the serum, tumor, and normal brain tissue were analyzed by high-pressure liquid chromatography. The etoposide concentration in the serum, tumor, and normal brain tissue peaked at 30 min in both groups. The serum concentration was similar between the two groups. The etoposide concentration in the tumor was at least 2.2 times higher in the IHIC group than in the IC group at 30 min and 2 hr. The area under drug concentration curve (AUC) in the tumor in the IHIC group was about 2.2 times higher than that in the IC group. The etoposide concentration in the normal brain on the drug injection side changed only slightly from 0.5 hr to 4 hr and was about 3 times higher in the IHIC group than in the IC group. The etoposide concentration in the contralateral normal brain was very low in both groups at 30 min and disappeared thereafter.

Intracarotid injection of anticancer drugs with AT II-induced hypertension further increases the drug concentration and AUC in the tumor compared with intracarotid injection alone and can be useful in treatment of malignant brain tumors.