Enzyme‐ and transporter‐mediated beverage–drug interactions: An update on fruit juices and green tea

Abstract

Beverage-drug interactions have remained an active area of research and have been the subject of extensive investigations in the past 2 decades. The known mechanisms of clinically relevant beverage-drug interactions include modulation of the activity of cytochrome P450 (CYP) 3A and organic anion-transporting polypeptide (OATP). For CYP3A-mediated beverage-drug interaction, the in vivo CYP3A inhibitory effect is limited to grapefruit juice (GFJ), which increases the bioavailability of several orally administered drugs that undergo extensive first-pass metabolism via enteric CYP3A. In contrast, clinically significant OATP-mediated beverage-drug interactions have been observed with not only GFJ but also orange juice, apple juice, and, most recently, green tea. Fruit juices and green tea are all a mixture of a large number of constituents. The investigation of specific constituent(s) responsible for the enzyme and/or transporter inhibition remains an active area of research, and many new findings have been obtained on this subject in the past several years. This review highlights the multiple mechanisms through which beverages can alter drug disposition and provides an update on the new findings of beverage-drug interactions, with a focus on fruit juices and green tea.

Safety, Efficacy, and Mechanistic Studies Regarding Citrus aurantium (Bitter Orange) Extract and p‐Synephrine

“…Grapefruit ( Citrus paradisi ) juice is known for its ability to alter drug metabolism through inhibition of cytochrome P450‐3A4 and results in drug–food interactions that may be life threatening (An et al ., ). The primary active ingredients in Citrus responsible for these effects are the furanocoumarins bergapten, bergamottin, and 6′,7′‐dihydroxybergamottin (Guo et al ., ; Paine et al ., ; Fujita et al ., ; Messer et al ., ; Greenblatt et al ., ).…”

Effects of soy containing diet and isoflavones on cytochrome P450 enzyme expression and activity

“…This was amply demonstrated in an early study in rabbits by Pineau et al (1991) which revealed large increases in CYP3A6 expression and activity associated with switch of diet from breast milk to solid diets at weaning. Subsequently, many investigators have focused on the CYP-regulatory effects of specific dietary components including dietary fats (reviewed by Hardwick et al, 2009); ethanol (reviewed by Ingelman-Sundberg et al, 1994; Ronis et al, 1996; Li and Cederbaum 2008) and phytochemicals in fruits and vegetables (reviewed by Ioannides, 1999; Lamps and Petersen, 2002; Murray 2006; Rodriguez-Fragoso et al, 2011; An et al 2015). In addition, a significant amount of work has examined the effects of dietary protein composition, in particular soy protein and its associated phytochemicals, on CYP expression and activity.…”

Pharmacokinetic drug-drug interactions of tyrosine kinase inhibitors: A focus on cytochrome P450, transporters, and acid suppression therapy

“…Fruit juice (GFJ, OJ, and OJ) inhibition of the organic anion‐transporting polypeptides (influx transporter at the intestinal and hepatic levels) also led to significant drug interactions. Interactions of fruit juices with P‐gp have also been reported, but the effect is minimal with no evidence of clinically relevant interactions . Very recently, inhibition of fruit juices and green tea on BCRP has been demonstrated in vitro with dasatinib as a dual substrate of P‐gp and BCRP .…”