The role of competitive binding to human serum albumin on efavirenz–warfarin interaction: a nuclear magnetic resonance study

The potential for co-prescription of the anti-human immunodeficiency virus (anti-HIV) drug efavirenz (EFV) and the oral anticoagulant warfarin (WAR) is currently high as EFV is a drug of choice for HIV type 1 infection and because cardiovascular disease is increasing among HIV-infected individuals. However, clinical reports of EFV–WAR interaction, leading to WAR overdosing, call for elucidation of the mechanisms involved in this drug–drug interaction. Here we present the first report demonstrating competition of the two drugs for the same binding site of human serum albumin. Using ligand-based nuclear magnetic resonance experiments, this study proves that EFV has an effect on the concentration of free WAR. This previously unidentified EFV–WAR interaction represents a potential risk factor that should be taken into account when considering treatment options.