title: Inflammation-mediated changes in drug transporter expression/activity: implications for therapeutic drug response.
abstract: Inflammation plays a critical role in host defense, maintaining cellular and tissue integrity following chemical, physical and biological insults. Inflammation presents in a variety of acute and chronic disease states and can contribute to disease resolution or progression depending upon the type, magnitude and duration of response. Importantly, it has been shown to modulate pharmacokinetic processes leading to variability in therapeutic drug response. Membrane-associated drug transporters are important determinants of drug disposition and pharmacokinetics and we, among others, have identified inflammation-mediated changes in their expression and regulation. Here, we discuss the current state of knowledge on drug transporter expression during acute and chronic inflammatory conditions and postulate how the altered expression of these transporters may modify the pharmacokinetics and pharmacodynamics of clinically important therapeutics. As understanding determinants of interpatient variability in therapeutic drug response is essential to the practice of medicine, this area of research warrants future clinical focus.
authors.affiliation: Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, 144 College Street, Toronto, ON, M5S 3M2, Canada.
authors.forename: Alexander M
authors.initials: AM
authors.lastname: Cressman
authors.forename: Vanja
authors.initials: V
authors.lastname: Petrovic
authors.forename: Micheline
authors.initials: M
authors.lastname: Piquette-Miller
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000235:genetics / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D018836:Inflammation Mediators / Q000008:administration & dosage / Q000378:metabolism / Q000502:physiology*; D026901:Membrane Transport Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D004364:Pharmaceutical Preparations / Q000008:administration & dosage / Q000378:metabolism*; D016896:Treatment Outcome
chemical_list: D018836:Inflammation Mediators; D026901:Membrane Transport Proteins; D004364:Pharmaceutical Preparations