Influence of halothane anaesthesia on protein binding of drugs

Abstract

We have read the recent report by Vorun et al.[1] "Variation in the binding affinity of warfarin and phenprocoumon to human serum albumin in relation to surgery". They found that the binding affinity of warfarin was reduced in serum samples taken during three days after surgery, Although during surgery the serum concentrations of fatty acid (NEFA) increased markedly, the effect on the binding affinity of oral anticoagulants was surprisingly small. None of the patients was given drugs that could have affected the protein binding of warfarin. Therefore, the influence of a competing ligand was not taken into consideration. However, drugs used during surgery were not considered.We have shown that anaesthetic agents can alter the protein binding of warfarin [2]. In patients undergoing cholecystectomy, we found an increase in the percentage of unbound warfarin 24 h after halothane anaesthesia. Even after 48 h, the percentage of unbound warfarin was still higher than control. Thus, our results are similar to those of Vorun et al. Halothane is metabolished in vivo to trifluoroacetic acid, which can displace drugs from binding sites on serum albumin. Concentrations of trifluoroacetic acid ranging from 0.8 to 2.6 mmol-1-1 have been found in serum from patients 24 h after halothane anaesthesia [3]. The effect of halothane anaesthesia on the protein binding of benzodiazepines [4] and thiopental [5] has also been described.We often forget the possible participation of volatile agents in drug interactions because they are quickly eliminated by the lungs. Binding of warfarin is an important determinant of dose requirement and adverse effects, and we think that the study of Vorun et al. is interesting; however, we suggest that they should give more specific information about anaesthetic drugs.