The complexities of antiretroviral drug-drug interactions: role of ABC and SLC transporters.
Treatment of human immunodeficiency virus (HIV) infection involves a combination of several antiviral agents belonging to different pharmacological classes. This combination is referred to as highly active antiretroviral therapy (HAART). This treatment has proved to be very effective in suppressing HIV replication, but antiretroviral drugs have complex pharmacokinetic properties involving extensive drug metabolism and transport by membrane-associated drug carriers. Combination drug therapy often introduces complex drug-drug interactions that can result in toxic or sub-therapeutic drug concentrations, compromising treatment. This review focuses on the role of ATP-binding cassette (ABC) membrane-associated efflux transporters and solute carrier (SLC) uptake transporters in antiretroviral drug disposition, and identifies clinically important antiretroviral drug-drug interactions associated with changes in drug transport.
Kis
Olena
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Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, 144 College Street, Room 1001, Toronto M5S3M2, Ontario, Canada.
Robillard
Kevin
K
Chan
Gary N Y
GN
Bendayan
Reina
R
D018528:ATP-Binding Cassette Transporters / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D019380:Anti-HIV Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D001692:Biological Transport / Q000187:drug effects; D004347:Drug Interactions; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D026901:Membrane Transport Proteins / Q000187:drug effects* / Q000378:metabolism
D018528:ATP-Binding Cassette Transporters; D019380:Anti-HIV Agents; D026901:Membrane Transport Proteins