19F NMR studies of enflurane elimination and metabolism

The elimination and metabolism of enflurane, a fluorinated ether anaesthetic, was studied by 19F NMR in vivo in both rat liver and brain as well as human body fluids. In the liver of thiobarbitone-anaesthetized rats the half-life for enflurane following exposure to 0.15% (v/v) for 30 min was 76 min but this could be decreased to 39 min by pretreatment of the animals with isoniazid (0.1% in the drinking water for 7 days), an agent known to enhance enflurane metabolism. In these animals the major organic metabolite difluoromethoxy difluoroacetate (DFMDFA) was also detected by 19F NMR in vivo. This metabolite was detected along with fluoride ion in rat and human urine and plasma by high resolution 19F NMR. Human urine also contained signals from a probable DFMDFA conjugate and unexpectedly from trifluoroacetate.