Interaction of isoflurane with the binding of drugs to proteins in serum and liver cell cytosol. An in vitro study.

The influence of isoflurane on the binding to human serum and isolated human serum albumin (HSA), of drugs (diazepam, phenytoin and warfarin) highly bound to serum proteins, was studied in vitro by equilibrium dialysis. Distribution dialysis was used to determine the effect of isoflurane on the concomitant binding of the drugs to human serum and rat liver cytosol. Isoflurane (3.3% and 5%) significantly suppressed the binding of diazepam only to HSA by 70 and 81%, respectively. Under clinically relevant experimental conditions, isoflurane increased the free fractions of diazepam and phenytoin by 16 and 11%, respectively. During distribution dialysis 5% of the anaesthetic decreased the binding of both diazepam and phenytoin to human serum by 55%, whereas drug binding to liver cytosol was decreased by 36% for diazepam only. Isoflurane exercised no significant effect on the protein binding of warfarin. It is concluded that any interactions with drug protein binding during isoflurane anaesthesia are unlikely to be of clinical significance.