Physiological Disposition of Pentobarbital in Tumor-bearing Mice1

Pentobarbital depressed macromolecular synthesis in Ehrlich ascites cells in vitro, and this depression was proportional to a decrease in oxygen consumption. How ever, survival time of animals bearing Ehrlich ascites cells was unaffected by pentobarbital. The acute toxicity of the drug was greatly enhanced by the presence of the tumor. Sleeping time was prolonged in mice carrying the following tumors: Ehrlich ascites. Sarcoma 180 ascites, and Yancey plasma cell solid. Seven-day Ehrlich ascites tumor-bearing animals treated with pentobarbital slept about three times longer than normal mice, but both groups awoke at the same plasma levels of the unbound drug. The plasma half-life of unchanged pentobarbital was about four times as long in tumor-bearing mice as it was in controls. No qualitative difference in catabolism other than rate was detected. Renal excretion of unchanged pentobarbital in tumor-bearing animals was 50% of control animals during the first 4 hr. In tumor-bearing mice the sleeping time of the nonmetabo ble barbiturate, barbital, was identical with that in normal animals. These data suggest that the tumor affected mainly pentobarbital metabolism. Tumor-bearing mice still responded to the pharmacological challenge of phénobarbitalwith the apparent induction of drug metabo lizing enzymes. The prolonged pentobarbital sleeping time in tumor-bearing mice required the development of some type of tumor-host relationship.