TY - JOUR T1 - A COMPARISON OF THE EFFECTS OF HALOTHANE AND CCl<sub>4</sub> ON THE HEPATIC DRUG METABOLIZING SYSTEM JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 556 LP - 566 VL - 177 IS - 3 AU - DONALD C. DAVIS AU - DAVID H. SCHROEDER AU - THEODORE E. GRAM AU - REGINALD L. REAGAN AU - JAMES R. GILLETTE Y1 - 1971/06/01 UR - http://jpet.aspetjournals.org/content/177/3/556.abstract N2 - An investigation was undertaken to compare the effects of halothane and CCl4 on various components of the drug metabolism system in hepatic microsomes and to study the influence of phenobarbital pretreatment on these effects. Groups of rats were pretreated with saline or phenobarbital (50 mg/kg i.p.) for three days. Some animals received halothane (1 nil/kg i.p.) on days 4 and 5 whereas other animals received CCl4 (0.4 ml/kg) on day 5. The animals were sacrificed 24 hours later. Both halothane and CCl4 significantly decreased microsomal ethylmorphine demethylase, reduced nicotinamide adenine dinucleotide phosphate-cyto-chrome c reductase and cytochrome P-450, but the effects were considerably less pronounced with halothane. Aniline hydroxylase activity was impaired by CCl4 treatment but not by halothane. After phenobarbital pretreatment, halothane had no significant effect on microsomal enzyme activities, but the effects of CCl4 were enhanced. Thus, although impairment of microsomal drug metabolism by CCl4 appears to be mediated by an active metabolite whose formation is stimulated by phenobarbital pretreatment, halothane may act through a different mechanism. © 1971 by The Williams &amp; Wilkins Co. ER -