Contrasting effects of halothane, isoflurane, and enflurane on in vivo drug metabolism in the rat.
Inhalational anesthetics might affect perioperative drug elimination by alterations in distribution, hepatic blood flow, or metabolism. The purpose of our study was to investigate the effects of inhalational anesthetics on drug metabolism in vivo during the pre- and postanesthetic periods. The aminopyrine breath test was used as a sensitive non-invasive index of drug metabolism, when the rate of elimination of 14CO2 in the exhaled breath of rats was measured after the intravenous administration of (N-dimethyl-14C) aminopyrine. The rate of aminopyrine metabolism was determined on three occasions in each rat; on the day prior to anesthesia and again 2 and 24 hr after anesthesia. The rats were anesthetized for 2 hr with halothane (0.125%, 0.25%, or 1.0%), enflurane (1.8%), or isoflurane (1.3%) in air. Halothane (P less than 0.05) prolonged aminopyrine half-life both 2 and 24 hr after anesthesia. This was a dose-dependent effect with higher concentrations of halothane causing greater impairment of aminopyrine metabolism 24 hr after anesthesia. Halothane (1.0%) increased the aminopyrine half-life from 41.3 +/- 0.9 min to 54.6 +/- 3.5 min 2 hr after anesthesia and to 54.0 +/- 3.5 min 24 hr after anesthesia. Although isoflurane (1.3%) caused a slight prolongation (P less than 0.05) of aminopyrine half-life 2 hr after anesthesia, this effect had disappeared by 24 hr. Enflurane (1.8%) did not affect aminopyrine elimination. Our results imply that volatile anesthetics may reduce the elimination of drugs given in the perioperative period and that differences may exist among anesthetic agents.
D000632:Aminopyrine / Q000378:metabolism; D000769:Anesthesia, Inhalation; D000818:Animals; D001944:Breath Tests; D004347:Drug Interactions; D004737:Enflurane / Q000494:pharmacology*; D006207:Half-Life; D006221:Halothane / Q000494:pharmacology*; D007530:Isoflurane / Q000494:pharmacology*; D008297:Male; D008738:Methyl Ethers / Q000494:pharmacology*; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D008738:Methyl Ethers; D004364:Pharmaceutical Preparations; D000632:Aminopyrine; D004737:Enflurane; D007530:Isoflurane; D006221:Halothane