BRAIN AND BLOOD-CONCENTRATIONS OF PROPOFOL AFTER RAPID INTRAVENOUS-INJECTION IN SHEEP, AND THEIR RELATIONSHIPS TO CEREBRAL EFFECTS

The time-course of propofol concentrations in the blood and brain foll owing rapid administration of three doses were examined using a sheep preparation and regional pharmacokinetic techniques. These were compar ed to the timecourse of cerebral effects of propofol reported previous ly. There were marked differences between the time-course of propofol concentrations in arterial blood and the brain, with a close relations hip between the time-course of brain concentrations and effects on dep th of anaesthesia and CPP There was evidence that the effect of propof ol on cerebral bloodflow altered its own rate of elution from the brai n. Hysteresis between arterial propofol concentrations and cerebral ef fects following rapid IV administration therefore appears to have a ph armacokinetic basis, and conventional compartmental pharmacokinetic an alysis using blood concentrations alone may fail to accurately predict the time-course of both brain propofol concentrations and depth of an aesthesia.