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.
Centro de Química Estrutural, Instituto Superior Técnico, Universidade de Lisboa, 1049-001 Lisbon, Portugal. Electronic address: riccardowanke@ist.utl.pt.
Riccardo
R
Wanke
Shrika G
SG
Harjivan
Sofia A
SA
Pereira
M Matilde
MM
Marques
Alexandra M M
AM
Antunes
D000480:Alkynes; D019380:Anti-HIV Agents / Q000493:pharmacokinetics*; D000925:Anticoagulants / Q000493:pharmacokinetics*; D048588:Benzoxazines / Q000493:pharmacokinetics*; D001667:Binding, Competitive; D003521:Cyclopropanes; D004347:Drug Interactions; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D012709:Serum Albumin / Q000378:metabolism*; D000075462:Serum Albumin, Human; D014859:Warfarin / Q000493:pharmacokinetics*
C422455:ALB protein, human; D000480:Alkynes; D019380:Anti-HIV Agents; D000925:Anticoagulants; D048588:Benzoxazines; D003521:Cyclopropanes; D012709:Serum Albumin; D014859:Warfarin; C098320:efavirenz; D000075462:Serum Albumin, Human
Drug–drug interactions; Drug–protein binding; Efavirenz; Human serum albumin; NMR; Warfarin