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[Pharmacokinetic study of tegafur in the hepatic tissue obtained from the patients with liver cancer].

SF-SP capsules, containing sustained release granules of tegafur, were given to 17 patients with liver cancer (5 primary and 12 metastatic), and tissue levels of tegafur and its metabolites, inhibition of thymidylate synthetase were examined. 5-FU and FdUMP, the active metabolites of tegafur, showed a good accumulation in hepatic lesion and their levels were found to be higher in patients with primary lesion than in metastatic one. In contrast, inhibitory rate of thymidylate synthetase in metastatic lesion was larger than in primary one, suggesting that the agent has stronger antitumor effect against metastatic lesion. This result is consistent with our clinical experiences. No clear relationship between tissue level of tegafur or its metabolites and inhibitory rate of thymidylate synthetase was found. Inhibition of DNA synthesis and/or RNA function are thought to be the action mechanisms of 5-FU and its derivatives. The present study suggests that measurement of the inhibition of thymidylate synthetase in malignant tissue together with the concentration of the drug and its metabolites may contribute for the elucidation of the antitumor effect of the drug.