Electronic Thesis and Dissertation Repository

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.

Available for download on Thursday, July 19, 2018

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