Formaldehyde formation as a metabolite of methoxyflurane.
The production of formaldehyde as a metabolite of enzymatic biotransformation of methoxyflurane was observed in vitro in hepatic microsomal preparations derived from Japanese monkeys, rabbits and Wistar strain rats. Production rates of formaldehyde were 0.80-2.50 n moles/mg protein/min in the induced group which was pretreated with phenobarbitone, and 0.15-0.68 n moles/mg protein/min in the non-induced group. This reaction needed the presence of NADPH and oxygen. Formaldehyde production was almost completely inhibited by addition of 25% CO. Further degradation of formaldehyde did not occur in microsomal suspension. No detectable species difference was observed among the animals used in this study. These results indicate that the biotransformation of methoxyflurane is preceded by interaction with cytochrome p-450 in hepatic microsomes in the presence of NADPH and oxygen.
D000818:Animals; D002248:Carbon Monoxide / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System; D005557:Formaldehyde / Q000096:biosynthesis*; D000882:Haplorhini; D008297:Male; D008733:Methoxyflurane / Q000378:metabolism*; D008862:Microsomes, Liver / Q000378:metabolism; D009249:NADP; D010100:Oxygen; D010634:Phenobarbital / Q000494:pharmacology; D011817:Rabbits; D051381:Rats
D005557:Formaldehyde; D008733:Methoxyflurane; D009249:NADP; D002248:Carbon Monoxide; D003577:Cytochrome P-450 Enzyme System; D010100:Oxygen; D010634:Phenobarbital