Impairment of drug metabolism in patients with liver cancer

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Abstract
Drug metabolizing capacity was investigated in sixteen patients with cancer in the liver by comparing in vivo (antipyrine disappearance rate from plasma) and in vitro (cytochrome P‐450, benzpyrene hydroxylase, and 7‐ethoxycoumarin O‐deethylase activities in liver biopsies) indices of drug metabolism with the condition of tumour‐free liver parenchyma and with biochemical liver function tests. Drug metabolism was impaired as antipyrine hydroxylation was significantly lower than in matched controls. Impairment of antipyrine metabolism was related to the pathological changes in the liver; patients with metastatic liver cancer or with tumour and cirrhosis metabolized antipyrine at a reduced rate, whereas those with a hepatoma occupying from 20 to 80% of the liver volume had normal antipyrine metabolism. Liver enzyme activities were related to the site of the biopsy; values were low in and around the tumour tissue and high in normal parenchyma. The antipyrine half‐life was related to serum albumin concentration but not to other liver function tests. The results demonstrate that in liver cancer patients the drug‐hydroxylating capacity is dependent on the ability of the tumour‐free parenchyma to metabolize drugs. Hence quantitative evaluation of liver changes together with tests measuring liver synthetic capacity might be of significance when predicting drug metabolism in patients with hepatic malignancy.