Effect of inhalation anesthetics on antipyrine pharmacokinetics of mice.

The effects of the volatile anesthetics, enflurane, isoflurane and halothane, on the pharmacokinetics of antipyrine were examined in mice. The administration of 0.75% isoflurane or 1.0% enflurane in air resulted in a 173 and a 206% increase, respectively, in antipyrine plasma half-life and a 29.1 and a 41.2% decrease in antipyrine total body clearance. There was also an almost 2-fold increase in the volume of distribution of antipyrine. Halothane, at 0.5% in air, had no significant effect upon antipyrine plasma half-life or its volume of distribution. There was no significant change in antipyrine total body clearance and volume of distribution 4 hr after exposure to the volatile agents, but there was a small increase in half-life. The exposures to the volatile anesthetics were also carried out in an atmosphere of 8% oxygen. Antipyrine plasma half-life was increased significantly by 48% in mice breathing 8% oxygen, compared to mice breathing air. Isoflurane in 8% oxygen increased the plasma half-life of antipyrine by 296% compared to mice breathing 8% oxygen. This increase was greater than the effect of isoflurane seen in mice breathing air. Mice breathing halothane in 8% oxygen exhibited a 21% increase in antipyrine plasma half-life and mice breathing enflurane in 8% oxygen, a 117% increase in antipyrine plasma half-life, although the changes were not markedly different from those seen in mice breathing air. Enflurane and isoflurane produced a significant increase in the volume of distribution for antipyrine in the mice breathing 8% oxygen. Total body clearance of antipyrine was decreased markedly in mice breathing isoflurane and enflurane but showed a lesser decrease in mice breathing halothane in 8% oxygen. In vitro in mouse microsomes, halothane, enflurane and isoflurane were all inhibitors of aminopyrine metabolism. Possible mechanisms for these results are discussed.