Rats and mice transplanted with different solid or ascites tumors are more sensitive than controls to the paralyzing effect of zoxazolamine and to the hypnotic action of pentobarbital. This increased effectiveness of pentobarbital can be partly explained by the fact that tumor-bearing animals show, in relation to controls, higher serum and brain concentrations of these two drugs. Other experiments indicate that zoxazolamine is less metabolized "in vitro" when incubated with liver homogenates obtained from tumor-bearing animals relative to controls. Also other substrates of liver microsomal enzymes, such as aniline, p-nitro-anisol and amidopyrine, are metabolized to a lesser extent, per unit of liver proteins, in tumor-bearing vs. control animals. In the case of pentobarbital, it is demonstrated that the impairment of metabolism is not the only factor responsible for the increased effect of pentobarbital in tumor-bearing animals because the onset of the narcosis is present at lower concentrations of brain pentobarbital as compared to controls. The surgical removal of the tumor abolishes the impairment of drug metabolism. Preliminary experiments seem to indicate that the serum of tumor-bearing animals contains principle(s) able to inhibit the activity of the microsomal liver enzymes.
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