Regulation of drug-metabolizing enzymes in infectious and inflammatory disease: implications for biologics–small molecule drug interactions. (3rd June 2017)

• Record Type: Journal Article
• Authors: Mallick, Pankajini; Taneja, Guncha; Moorthy, Bhagavatula; Ghose, Romi
• Is Part Of: Expert opinion on drug metabolism and toxicology. Volume 13:Number 6(2017:Jun.)
• Page Start: 605
• Page End: 616
• Publication Date: 2017-06-03
• Subjects: Biologics -- small molecule drugs -- drug-drug interaction -- drug metabolizing enzymes -- cytokines -- inflammation -- infection -- toll-like receptors -- nuclear receptors -- interferon; Drugs -- Toxicology -- Periodicals; Drugs -- Metabolism -- Periodicals; 615.7
• DOI: 10.1080/17425255.2017.1292251
• Languages: English
• ISSNs: 1742-5255

Abstract

ABSTRACT: Introduction: Drug-metabolizing enzymes (DMEs) are primarily down-regulated during infectious and inflammatory diseases, leading to disruption in the metabolism of small molecule drugs (smds), which are increasingly being prescribed therapeutically in combination with biologics for a number of chronic diseases. The biologics may exert pro- or anti-inflammatory effect, which may in turn affect the expression/activity of DMEs. Thus, patients with infectious/inflammatory diseases undergoing biologic/smd treatment can have complex changes in DMEs due to combined effects of the disease and treatment. Areas covered: We will discuss clinical biologics-SMD interaction and regulation of DMEs during infection and inflammatory diseases. Mechanistic studies will be discussed and consequences on biologic-small molecule combination therapy on disease outcome due to changes in drug metabolism will be highlighted. Expert opinion: The involvement of immunomodulatory mediators in biologic-SMDs is well known. Regulatory guidelines recommend appropriate in vitro or in vivo assessments for possible interactions. The role of cytokines in biologic-SMDs has been documented. However, the mechanisms of drug-drug interactions is much more complex, and is probably multi-factorial. Studies aimed at understanding the mechanism by which biologics effect the DMEs during inflammation/infection are clinically important.