The interaction of enflurane, halothane and the halothane metabolite trifluoroacetic acid with the binding of acidic drugs to human serum albumin. An in vitro study.
The interaction of the volatile anaesthetics enflurane, halothane and the halothane metabolite trifluoroacetic acid with the binding of two highly bound acidic drugs (warfarin, phenytoin) to albumin has been studied in vitro by equilibrium dialysis. Trifluoroacetic acid (TFA) inhibited the binding of both drugs to human serum albumin (HSA). Halothane, on the other hand, increased the binding of warfarin to HSA, while enflurane inhibited only the binding of phenytoin. It seems that the binding of the acidic drugs warfarin and phenytoin to HSA is more sensitive to the structures of the gases than for the basic drug diazepam which was previously shown to be equally affected by both gases. Furthermore, it seems that drugs competing for the same binding site (warfarin, phenytoin) may respond differently to conformational changes of the site. It is suggested that drugs bound to the "diazepam site" are more easily affected by the volatile anaesthetics than drugs bound to the "warfarin site".
D001665:Binding Sites / Q000187:drug effects; D001667:Binding, Competitive; D004737:Enflurane / Q000494:pharmacology*; D005463:Fluoroacetates / Q000494:pharmacology*; D006221:Halothane / Q000494:pharmacology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D008956:Models, Chemical; D010672:Phenytoin / Q000097:blood; D011485:Protein Binding / Q000187:drug effects; D012709:Serum Albumin / Q000378:metabolism*; D014269:Trifluoroacetic Acid / Q000494:pharmacology*; D014859:Warfarin / Q000097:blood
D005463:Fluoroacetates; D012709:Serum Albumin; D014859:Warfarin; D010672:Phenytoin; D004737:Enflurane; D014269:Trifluoroacetic Acid; D006221:Halothane