Lack of effect of fever on antipyrine oxidation in the rat

The pharmacokinetics of 14C-antipyrine were studied in rats with fever induced by intracerebroventricular injections of prostaglandin E 1. The rats were used as their own controls with at least 5 days between the control and the fever period. The effect of temperature on rates of antipyrine metabolism (oxidation followed by conjugation) and paracetamol metabolism (conjugation) was aslo tested in suspensions of isolated liver cells. Fever increased the biological half-life of antipyrine to 147% of control values (P < 0.01) and the apparent volume of distribution to 113% of control values (P < 0.05). In individual rats the increase in biological half-life was almost counterbalanced by the increase in apparent volume of distribution, resulting in non-significant changes in the metabolic clearance of the drug. The half-life of antipyrine elimination in suspensions of isolated liver cells was not changed by increasing the temperature from 29 to 39°C. The half-life paracetamol elimination in suspensions of isolated liver cells decreased, however, when the temperature was increased from 29 to 39°C. The results suggest that antipyrine oxidation was not influenced by temperature changes in the range of moderate fever and that temperature changes affected different types of metabolic reactions differently.