Isoflurane increases the anaerobic metabolites of halothane.
The effect of isoflurane on the anaerobic metabolism of halothane to chlorodifluoroethene (CDE) and chlorotrifluoroethane (CTE) was studied with microsomes of guinea pig liver by gas chromatography. The reaction mixture used to measure the end products of anaerobic metabolism consisted of a microsomal suspension, 3 mM NADPH, halothane and isoflurane (except in control groups) in 0.1 M potassium phosphate buffer solution (pH 7.4). The Km values for CDE formation were 601.61 +/- 266.91, 254.22 +/- 86.58, 257.92 +/- 129.11, 268.55 +/- 125.66 and 319.22 +/- 86.76 microM (mean +/- SD, n = 5) at 0 mM (0%), 0.12 mM (0.26%), 0.29 mM (0.64%), 0.58 mM (1.30%) and 1.16 mM (2.59%) isoflurane, respectively. The Km values for CTE formation were 1204.74 +/- 551.64, 553.75 +/- 177.89, 521.14 +/- 249.77, 560.67 +/- 229.61 and 711.05 +/- 317.13 microM (n = 5) at 0 mM (0%), 0.12 mM (0.26%), 0.29 mM (0.64%), 0.58 mM (1.30%) and 1.16 mM (2.59%) isoflurane, respectively. In contrast, the Vmax values for CDE and CTE formation at these isoflurane concentrations were not significantly different than in the control groups. In this study the production of CDE and CTE was significantly (P < 0.05) increased by isoflurane, at concentrations up to 0.58 mM (1.30%).
Rahman
M
M
Department of Anesthesiology and Intensive Care Medicine, School of Medicine, Hiroshima University, Japan.
Fujii
K
K
Sato
N
N
Yuge
O
O
D000693:Anaerobiosis; D000818:Animals; D001711:Biotransformation; D056486:Chemical and Drug Induced Liver Injury / Q000473:pathology; D017402:Chlorofluorocarbons / Q000378:metabolism; D002849:Chromatography, Gas; D006168:Guinea Pigs; D006221:Halothane / Q000493:pharmacokinetics*; D066298:In Vitro Techniques; D007530:Isoflurane / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D013268:Stimulation, Chemical
D017402:Chlorofluorocarbons; D009249:NADP; C016304:chlorotrifluoroethylene; D007530:Isoflurane; C018483:2-chloro-1,1-difluoroethylene; D006221:Halothane