This study was to determine which of two routes of administration of 5-fluorouracil (5-FU) is more effective, by measuring the radioactvity in the body tissues of gastric cancer patients after the administration of 5-FU-l4C via the systemic intravenous and the regional intra-arterial routes. After the drug was administered intravenously in one group of patients, and intra-arterially in another; samples of portal venous blood, the liver, the lymph nodes, and the normal and the cancerous tissues of the stomach were obtained. The radioactivities of the samples were measured, and it was found that those of the regional lymph nodes, the liver, and the normal and the cancerous tissues of the stomach were much higher in the latter group. The regional intra-arterial routes is the more effective way to administer 5-FU in patients with stomach cancer.
Carbon Radioisotopes/diagnostic use ; Comparative Study ; Fluorouracil/administration & dosage ; Fluorouracil/metabolism* ; Human ; Injections, Intra-Arterial ; Injections, Intravenous ; Stomach Neoplasms/drug therapy* ; Stomach Neoplasms/metabolism

BACKGROUND: This study was designed to determine the relationship of propranolol pharmacokinetic parameters with portosystemic shunt in CCl4-induced cirrhotic rats. METHODS: Cirrhotic rats(n=6) were induced by intramuscular injection of CCl4 in olive oil(two time per weeks) for 12 weeks. Controls (n=6) were injected intramuscularly with the same dose of olive oil for 12 weeks. We evaluated the amount of portosystemic shunt by thallium-201 per rectal scintigraphy. After intravenous bolus injection of propranolol (2mg/kg) to rats, the serum propranolol concentrations were analyzed by a HPLC-fluorimetric detector system. Pharmacokinetic parameters such as C0, AUC, t(1/2(beta)), and CLp were determined in each group. Then, a small amount of heptic tissue was obtained and subjected to determination of the hepatic collagen content by quantitating 4-hydroxyproline and were inspected by microscope after hematoxylin and eosin stain. RESULTS: In liver biopsy, liver fibrosis progressed in CCl4-induced cirrhotic rats. The serum concentrations of propranolol were significantly (p < 0.01) elevated in CCl4-induced cirrhotic rats. Mean amount of 4-hydroxyproline, mean H/L ratio, and mean AUC in CCl4-induced cirrhotic rats was significantly (p < 0.01) higher than that in control rats. There was a relationship between AUC, H/L ratio, and amount of 4-hydroxyproline. CONCLUSION: H/L ratio may help in the selection of drug dosage (especially blood flow dependent drug) in pre-clinical studies for chronic liver disease during the drug development process.
Animals ; Carbon Tetrachloride Poisoning/*complications ; Chromatography, High Pressure Liquid ; English Abstract ; Liver Cirrhosis, Experimental/*metabolism/physiopathology ; Portal System/physiopathology ; Propranolol/*pharmacokinetics ; Rats ; Rats, Sprague-Dawley ; Thallium Radioisotopes/diagnostic use