Degree
Master of Science
Program
Physiology and Pharmacology
Supervisor
Dr. Rommel Tirona
Abstract
Fruit juice-drug interactions (FJDIs) involving non-metabolized oral medications result in decreased drug exposure that may lead to reduced therapeutic efficacy. The effect is thought to be mediated by inhibition of the intestinal drug transporters organic anion transporting polypeptide 1A2 and 2B1 (OATP1A2 and OATP2B1) by fruit juice constituents, however the exact mechanisms remain controversial. We tested the hypothesis that fruit juices limit the absorption of fexofenadine through interactions with specific intestinal transporters. In vitro transport and fruit juice inhibition studies using fexofenadine, a medication involved in FJDIs, revealed that in addition to previously implicated transporters, organic cation transporter 1 (OCT1) and organic solute transporter alpha/beta (OSTα/β) are potential novel targets of fruit juice components. Pharmacokinetic interaction studies in wild-type and mOatp2b1 knockout mice demonstrated that mOatp2b1 is not involved in fexofenadine absorption or FJDIs in vivo. These findings provide new insights into the mechanism of FJDIs.
Recommended Citation
Li, Mandy MJ, "Evaluating the role of intestinal transporters in fruit juice-drug interactions" (2016). Electronic Thesis and Dissertation Repository. 3849.
https://ir.lib.uwo.ca/etd/3849
Included in
Digestive, Oral, and Skin Physiology Commons, Human and Clinical Nutrition Commons, Medical Pharmacology Commons, Pharmacology Commons