Inflammation-mediated changes in drug transporter expression/activity: implications for therapeutic drug response
- 10 January 2012
- journal article
- review article
- Published by Taylor & Francis Ltd in Expert Review of Clinical Pharmacology
- Vol. 5 (1), 69-89
- https://doi.org/10.1586/ecp.11.66
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.Keywords
This publication has 100 references indexed in Scilit:
- Role of high-fat diet in regulation of gene expression of drug metabolizing enzymes and transportersLife Sciences, 2011
- Membrane transporters in drug developmentNature Reviews Drug Discovery, 2010
- Change in P-glycoprotein and caveolin protein expression in brain striatum capillaries in New Zealand Obese mice with type 2 diabetesLife Sciences, 2009
- Redundant roles for cJun-N-terminal kinase 1 and 2 in interleukin-1β-mediated reduction and modification of murine hepatic nuclear retinoid X receptor αJournal of Hepatology, 2009
- Impact of Infectious and Inflammatory Disease on Cytochrome P450–Mediated Drug Metabolism and PharmacokineticsClinical Pharmacology & Therapeutics, 2009
- Estimates of the prevalence of arthritis and other rheumatic conditions in the United States: Part IArthritis & Rheumatism, 2007
- Estimates of the prevalence of arthritis and other rheumatic conditions in the United States: Part IIArthritis & Rheumatism, 2007
- Downregulation of drug transport and metabolism in mice bearing extra-hepatic malignanciesBritish Journal of Cancer, 2007
- Nitric oxide differentially regulates renal ATP-binding cassette transporters during endotoxemiaPflügers Archiv - European Journal of Physiology, 2007
- Decreased blood–brain barrier permeability to fluorescein in streptozotocin-treated ratsNeuroscience Letters, 2007