Inhibitory effects of corticoids on reductive halothane dehalogenation.
The effects of corticoids, hydrocortisone, methylprednisolone, betamethasone and dexamethasone, on the reductive metabolism of halothane to produce chloro-difluoroethylene (CDE) and chlorotrifluoroethane (CTE) in the liver microsomes of guinea-pig were examined. The substrate differential spectrum for methylprednisolone showed a peak at 412 nm and trough at 395 nm, typical modified type II. The other corticoids showed a similar spectral change. The corticoids had no effect on NADPH-cytochrome P450 reductase. All of these corticoids inhibited the reductive dehalogenation of halothane. The concentrations of hydrocortisone, methylprednisolone, betamethasone and dexamethasone causing 50% inhibition of CDE formation from halothane were 5.1 +/- 0.7 mg/ml, 3.1 +/- 1.2 mg/ml, 2.3 +/- 0.4 mg/ml and 2.4 +/- 0.6 mg/ml, respectively, with no significant differences except for hydrocortisone. The concentrations of hydrocortisone, methylprednisolone, betamethasone and dexamethasone causing 50% inhibition of CTE formation from halothane were 4.9 +/- 0.5 mg/ml, 3.1 +/- 1.0 mg/ml, 2.4 +/- 0.3 mg/ml and 28.0 +/- 9.1 mg/ml, respectively, with no significant differences except for dexamethasone. Our results showed that corticoids inhibit halothane metabolism.
Fujii
K
K
Department of Anesthesiology and Critical Care Medicine, Hiroshima University School of Medicine, Japan.
D000305:Adrenal Cortex Hormones / Q000494:pharmacology*; D018685:Anesthetics, Inhalation / Q000378:metabolism*; D000818:Animals; D006168:Guinea Pigs; D006221:Halothane / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism; D010084:Oxidation-Reduction
D000305:Adrenal Cortex Hormones; D018685:Anesthetics, Inhalation; D009251:NADPH-Ferrihemoprotein Reductase; D006221:Halothane