Displacement of some basic drugs from human serum proteins by enflurane, halothane and their major metabolites. An in...

The influence of volatile anaesthetics (halothane, enflurane) on the serum protein binding of three highly bound basic drugs has been studied in vitro by equilibrium dialysis. Radioactive labelled isotopes were used for the determination of drug concentrations. Enflurane, halothane and the halothane metabolite trifluoroacetic acid (TFA) inhibited the binding of diazepam to serum and to its main binding protein, albumin. The binding of diazepam to albumin was inhibited in a competitive manner and was not related to the anaesthetic potency of the vapours. Thus the observed displacement of diazepam should be regarded as a side-effect of the volatile anaesthetics. The binding of propranolol and prazosin in serum was not significantly influenced by the investigated anaesthetics. At clinically relevant concentrations of the anaesthetics, diazepam was displaced significantly only by enflurane with an increase in free fraction of 60% in serum. TFA in concentrations seen after operation significantly increased the free fraction of diazepam up to 90%. We conclude that enflurane anaesthesia may temporarily potentiate the pharmacological effect of diazepam and that, in the postoperative period following halothane anaesthesia, a more rapid elimination of diazepam could be expected.