DISPLACEMENT OF SOME BASIC DRUGS FROM HUMAN SERUM PROTEINS BY ENFLURANE, HALOTHANE AND THEIR MAJOR METABOLITES

The influence of volatile anaesthetics (halothane, enflurane)on the serum protein binding of three highly bound basic drugshas been studied in vitro by equilibrium dialysis. Radioactivelabelled isotopes were used for the determination of drug concentrations.Enflurane, halothane and the halothane metabolite trifluoroaceticacid (TFA) inhibited the binding of diazepam to serum and toits main binding protein, albumin. The binding of diazepam toalbumin was inhibited in a competitive manner and was not relatedto the anaesthetic potency of the vapours. Thus the observeddisplacement of diazepam should be regarded as a side-effectof the volatile anaesthetics. The binding of propranolol andprazosin in serum was not significantly influenced by the investigatedanaesthetics. At clinically relevant concentrations of the anaesthetics,diazepam was displaced significantly only by enflurane withan increase in free fraction of 60% in serum. TFA in concentrationsseen after operation significantly increased te free fractionof diazepam up to 90%. We conclude that enflurane anaesthesiamay temporarily potentiate the pharmacological effect of diazepamand that, in the postoperuative period following halothane anaesthesia,a more rapid elimination of diazepam could be expected.