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

Abstract

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.

• Authors: Riccardo Wanke, Shrika G Harjivan, Sofia A Pereira, M Matilde Marques, Alexandra M M Antunes
• Journal: International journal of antimicrobial agents (Int J Antimicrob Agents) Vol. 42 Issue 5 Pg. 443-6 (Nov 2013) ISSN: 1872-7913 [Electronic] Netherlands
• PMID: 24051055 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

Chemical References

• ALB protein, human
• Alkynes
• Anti-HIV Agents
• Anticoagulants
• Benzoxazines
• Cyclopropanes
• Serum Albumin
• Warfarin
• efavirenz
• Serum Albumin, Human

Topics

• Alkynes
• Anti-HIV Agents (pharmacokinetics)
• Anticoagulants (pharmacokinetics)
• Benzoxazines (pharmacokinetics)
• Binding, Competitive
• Cyclopropanes
• Drug Interactions
• Humans
• Magnetic Resonance Spectroscopy
• Serum Albumin (metabolism)
• Serum Albumin, Human
• Warfarin (pharmacokinetics)