Inhibition of hepatic drug metabolism in VX2 carcinoma-bearing rabbits.

Hepatic metabolism of aniline, p-chloro-N-methylaniline, and aminopyrine was determined in control male, New Zealand White rabbits or those bearing VX2 carcinoma (a prostaglandin-secreting tumor). In addition, the levels of cyclic AMP and cyclic GMP in the liver and the concentration of calcium in serum were examined. After 13 days of tumor growth, metabolism of aminopyrine and PCMA was decreased by approximately 30%, whereas aniline metabolism was not significantly altered. Metabolism of all substrates was significantly depressed to 20-60% of control by 22 days after transplantation. Serum calcium levels increased by 14 and 29% after 13 and 22 days, respectively. The ratio of cyclic AMP to cyclic GMP was 156% of control after 13 days and 139% by 22 days of tumor growth. The increased ratio was due solely to a change in cyclic AMP concentration. A 20-min pretreatment with prostaglandin E1, 0.3 mg/kg ip, depressed in vitro hepatic metabolism of all substrates by 27-56% while increasing cyclic AMP levels by 42%.