Reevaluation of potency and pharmacokinetic properties of some lipid-soluble barbiturates with an EEG-threshold method.

Five lipid-soluble anaesthetic barbiturates amobarbital, (pentymalum NFN), hexobarbital (enhexymalum NFN), pentobarbital (mebumalum NFN), thiopental (thiomebumalum NFN), methohexital (enallynymalum NFN) were investigated for potency and kinetic properties with an EEG-threshold method. By constant infusion of barbiturate at different dose rates to a well specified EEG-criterion, the "silent second", a dose rate curve can be made. This curve has a minimum, "optimal dose rate", and the amount of barbiturate used to reach the criterion at this dose rate can be used as an accurate measure of potency. The dose to reach the "silent second" at the optimal dose rate was highly correlated to brain concentrations at the criterion for the barbiturates in contrast to the plasma concentrations. This measure of potency is superior to other used measures such as anaesthesia times or AD50, since it is less affected by differences in pharmacokinetic properties. The anaesthesia times after threshold determinations show large variations between different barbiturates which can be dependent both on dose administered and on dose rate. The quotient between brain concentration at the EEG-criterion and at the time of return of righting reflex for these barbiturates shows variations that can be due to differences in acute tolerance.