Abstract
Using rats, we studied how best to assess hepatic damage after administering therapeutic doses of each of five anti-cancer drugs or of the hepatotoxin, carbon tetrachloride. As indexes, we compared measurement of the concentration of administered antipyrine in plasma with measurement in serum of alpha-fetoprotein or of the activities of five enzymes that reportedly best reflect hepatic damage. The biological half-life of antipyrine in the plasma was increased more than threefold on pretreating the rats with any of the five cytotoxic drugs or with carbon tetrachloride. In contrast, the concentrations of alpha-fetoprotein, alkaline phosphatase, gamma-glutamyltransferase, or glutamate dehydrogenase were not consistently increased. Of the enzymes tested in serum, aspartate aminotransferase and ornithine carbamoyltransferase best indicated hepatic impairment resulting from the treatment with anti-cancer drugs. Our results imply that determination of the pharmacokinetics of marker drugs such as antipyrine better indicates hepatic dysfunction induced by cytotoxic agents than does measurement of the enzymes liberated into serum as a result of damage to liver mitochondria.
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