Van Dyke R A, Kooistra K L, Moses C J, Powis G
Biochem Pharmacol. 1987 Apr 1;36(7):1023-7. doi: 10.1016/0006-2952(87)90409-6.
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.
在小鼠中研究了挥发性麻醉剂恩氟烷、异氟烷和氟烷对安替比林药代动力学的影响。在空气中给予0.75%异氟烷或1.0%恩氟烷分别使安替比林血浆半衰期增加173%和206%，安替比林全身清除率分别降低29.1%和41.2%。安替比林的分布容积也增加了近2倍。空气中0.5%的氟烷对安替比林血浆半衰期或其分布容积无显著影响。暴露于挥发性药物4小时后，安替比林全身清除率和分布容积无显著变化，但半衰期略有增加。挥发性麻醉剂暴露也在8%氧气的气氛中进行。与呼吸空气的小鼠相比，呼吸8%氧气的小鼠安替比林血浆半衰期显著增加48%。与呼吸8%氧气的小鼠相比，8%氧气中的异氟烷使安替比林血浆半衰期增加296%。这种增加大于在呼吸空气的小鼠中观察到的异氟烷的作用。呼吸8%氧气的氟烷的小鼠安替比林血浆半衰期增加21%，呼吸8%氧气的恩氟烷的小鼠安替比林血浆半衰期增加117%，尽管这些变化与呼吸空气的小鼠中观察到的变化没有明显差异。恩氟烷和异氟烷使呼吸8%氧气的小鼠中安替比林的分布容积显著增加。呼吸异氟烷和恩氟烷的小鼠中安替比林的全身清除率显著降低，但呼吸8%氧气的氟烷的小鼠中降低较少。在小鼠微粒体的体外实验中，氟烷、恩氟烷和异氟烷都是氨基比林代谢的抑制剂。讨论了这些结果的可能机制。
