Influence of cimetidine and diethyldithiocarbamate on the metabolism of halothane and methoxyflurane in vitro.
The metabolism of halothane and methoxyflurane was measured in vitro by the vial equilibration method using the S-9-fraction from rat liver as source of enzymes. Kinetic values were measured for halothane: Vmax = 11.6 nmol/g.min, KM = 19.6 mumol/l and methoxyflurane: Vmax = 12.0 nmol/g.min, KM = 17.5 mumol/l. Dithiocarb showed strong inhibitory activity on halothane and methoxyflurane metabolism; inhibition constants were calculated as Ki = 0.051 mmol/l and Ki = 0.004 mmol/l, respectively. Cimetidine inhibited the metabolism of both anesthetics to a lesser extent. Inhibition constants were calculated as Ki = 16.2 mmol/l and Ki = 8.2 mmol/l for halothane and methoxyflurane, respectively. The observed inhibitory properties of dithiocarb and cimetidine on the metabolism of halothane and methoxyflurane may be of interest in connection with the problem of toxic liver and kidney injury after anesthesia with these agents.
Loesch
J
J
Department of Toxicology, Medical University of Lübeck, Federal Republic of Germany.
Siegers
C P
CP
Younes
M
M
D000818:Animals; D002849:Chromatography, Gas; D002927:Cimetidine / Q000494:pharmacology*; D004050:Ditiocarb / Q000494:pharmacology*; D006221:Halothane / Q000378:metabolism*; D066298:In Vitro Techniques; D008099:Liver / Q000201:enzymology / Q000378:metabolism; D008297:Male; D008733:Methoxyflurane / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D008733:Methoxyflurane; D002927:Cimetidine; D004050:Ditiocarb; D006221:Halothane