TY - JOUR
T1 - The role of competitive binding to human serum albumin on efavirenz-warfarin interaction
T2 - A nuclear magnetic resonance study
AU - Wanke, Riccardo
AU - Harjivan, Shrika G.
AU - Pereira, Sofia A.
AU - Marques, M. Matilde
AU - Antunes, Alexandra M.M.
N1 - Funding Information:
Funding: This work was supported in part by Fundação para a Ciência e a Tecnologia (FCT) [grants PTDC/QUI-QUI/113910/2009 and PEst-OE/QUI/UI0100/2013 ]. RW and SGH also thank FCT for fellowships SFRH/BPD/70953/2010 and SFRH/BD/80690/2011, respectively.
PY - 2013/11
Y1 - 2013/11
N2 - 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.
AB - 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.
KW - Drug-drug interactions
KW - Drug-protein binding
KW - Efavirenz
KW - Human serum albumin
KW - NMR
KW - Warfarin
UR - http://www.scopus.com/inward/record.url?scp=84885431678&partnerID=8YFLogxK
U2 - 10.1016/j.ijantimicag.2013.06.023
DO - 10.1016/j.ijantimicag.2013.06.023
M3 - Article
C2 - 24051055
AN - SCOPUS:84885431678
SN - 0924-8579
VL - 42
SP - 443
EP - 446
JO - International Journal Of Antimicrobial Agents
JF - International Journal Of Antimicrobial Agents
IS - 5
ER -