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.

Keywords::

• acute and chronic inflammation
• animal models
• ATP-binding cassette transporter superfamily
• gene regulation
• immunopharmacology
• pharmacokinetics
• solute carrier transporter family
• therapeutic drug response

Financial & competing interests disclosure

Research conducted by the authors was completed through funding provided by the Canadian Institutes of Health Research (CIHR grant #57688) and the National Cancer Institute of Canada. AM Cressman is the recipient of an Alexander Graham Bell Canada Graduate Scholarship Master’s Award from the Natural Science and Engineering Research Council of Canada. V Petrovic is the recipient of a Doctoral Research Award from the Canadian Institutes of Health Research and an Ontario Graduate Scholarship. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.