The effect of anti-cancer drugs on the plasma disposition of antipyrine and the biliary excretion of phenolphthalein in the rat

The uptake and plasma disposition of antipyrine in the rat have been examined as a possible model for estimating the metabolic effects caused by the administration of the cytotoxic anti-cancer drugs to man. Pretreatment of the rats with the anti-cancer drugs retarded and decreased absorption from the stomach and the elimination of antipyrine from the plasma was also considerably decreased. In parallel with these findings the marked reeduction in the biliary excretion of phenolphthalein indicated a decrease in hepatic function caused by the cytotoxic drugs. In vitro investigations appeared to suggest the most likely cause of the prolonged antipyrine plasma half-life was the reduction in hepatic cytochrome P450 content.