**2. Food-drug interactions**

A drug-nutrient interaction is defined as the result of a physical, chemical, physiological, or pathophysiological relationship between a drug and a nutrient [8,9]. An interaction is con‐ sidered significant from a clinical perspective if it alters the therapeutic response. Food-drug interactions can result in two main clinical effects: the decreased bioavailability of a drug, which predisposes to treatment failure, or an increased bioavailability, which increases the risk of adverse events and may even precipitate toxicities (See Figure 1) [4, 10,11].

**Figure 1.** Drug-fruit/vegetable interaction and effects on bioavailability of drugs. During the consumption of drugs with fruits or vegetables the **ADME** properties of drug (**A**bsorption, **D**istribution, **M**etabolism and **E**xcretion) can be modified by drug-phytochemical interaction. As a result of this interaction can be increased or decreased plasma con‐ centrations of a drug which can lead to the presence of adverse events or treatment failure.

Nutritional status and diet can affect drug action by altering metabolism and function. In addition, various dietary components can have pharmacological activity under certain cir‐ cumstances [12]. For healthy-treatment intervention, it is necessary to understand how these drug-food interactions can induce a beneficial result or lead to detrimental therapeutic con‐ ditions (less therapeutic action or more toxicity). Drug-drug interactions are widely recog‐ nized and evaluated as part of the drug-approval process, whether pharmaceutical, pharmacokinetic, or pharmacodynamic in nature. Equal attention must be paid to food-drug interactions (Figure 2).

malnutrition, gastrointestinal tract dysfunctions, acquired immunodeficiency syndrome and chronic diseases that require the use of multiple drugs, as well as those receiving enteral nu‐ trition or transplants. Therefore, the main reason for devoting a major review to nutrientdrug interactions is the enormous importance of fruits and vegetables used for their beneficial effects as nutrients and as components in folk medicine. There are currently few studies that combine a nutrient-based and detailed pharmacological approach [4], or studies

A drug-nutrient interaction is defined as the result of a physical, chemical, physiological, or pathophysiological relationship between a drug and a nutrient [8,9]. An interaction is con‐ sidered significant from a clinical perspective if it alters the therapeutic response. Food-drug interactions can result in two main clinical effects: the decreased bioavailability of a drug, which predisposes to treatment failure, or an increased bioavailability, which increases the

**Figure 1.** Drug-fruit/vegetable interaction and effects on bioavailability of drugs. During the consumption of drugs with fruits or vegetables the **ADME** properties of drug (**A**bsorption, **D**istribution, **M**etabolism and **E**xcretion) can be modified by drug-phytochemical interaction. As a result of this interaction can be increased or decreased plasma con‐

centrations of a drug which can lead to the presence of adverse events or treatment failure.

risk of adverse events and may even precipitate toxicities (See Figure 1) [4, 10,11].

that systematically explore the risk and benefits of fruit and vegetables [5-7].

**2. Food-drug interactions**

2 Drug Discovery

**Figure 2.** Bioassay models for studying drug-phytochemical interaction.

There are four types of accepted drug-food interactions based on their nature and mecha‐ nisms.

porters (ENT, SLC29), the concentrative nucleoside transporters (CNT, SLC28), the apical

Until recently, little regard was given to the possibility that food and food components could cause significant changes to the extent of drug absorption via effects on intestinal and liver transporters. It is now well known that drug-food interactions might affect the pharma‐ cokinetics of prescribed drugs when co-administered with food [24]. Common foods, such as fruits and vegetables, contain a large variety of secondary metabolites known as phyto‐ chemicals (Tabla 1), many of which have been associated with health benefits [25]. However, we know little about the processes through which these phytochemicals (and/or their me‐ tabolites) are absorbed into the body, reach their biological target, and are eliminated. Re‐ cent studies show that some of these phytochemicals are substrates and modulators of specific members of the superfamily of ABC transporting proteins [26]. Indeed, *in vitro* and preclinical data in rats suggest that a variety of foodstuffs [27,28], including herbal teas [29,30] and vegetables and herbs [31,32] can modulate the activity of drug transporters. It is not yet known whether these effects are predictive of what will be observed clinically.

It has been shown that, before reaching the systemic circulation, the metabolism of orally in‐ gested drugs ('first-pass metabolism' or 'presystemic clearance') has clinically relevant influ‐ ences on the potency and efficacy of drugs. Both the intestine and liver account for the presystemic metabolism in humans. Drug metabolism reactions are generally grouped into 2 phases. Phase I reactions involve changes such as oxidation, reduction, and hydrolysis and are primarily mediated by the cytochrome P450 (CYP) family of enzymes. Phase II reactions use an endogenous compound such as glucuronic acid, glutathione, or sulfate, to conjugate with the drug or its phase I–derived metabolite to produce a more polar end product that

relevance of drug transport for clinical pharmacokinetics.

**4. Foods and drug-metabolizing enzyme**

can be more readily excreted [33].

−dependent bile salt transporter (ASBT, SLC10), the monocarboxylate transporters (MCT, SLC16), and the peptide transporters (PEPT, SLC15) [21]. The SLCO family is made up of the organic anion transporting polypeptides (OATP) [22]. Efflux transporters ex‐ pressed in the intestine and liver include P-glycoprotein (Pgp, ABCB1), bile salt export pump (BSEP, ABCB11), multidrug resistance proteins (MRP1- 6, ABCC1-6), and breast can‐ cer resistance protein (BCRP, ABCG2), all members of the ATP-Binding Cassette superfami‐ ly (ABC transporters) [23]. Members of this superfamily use ATP as an energy source, allowing them to pump substrates against a concentration gradient. In the liver, uptake transporters are mainly expressed in the sinusoid, and excretion transporters are mainly ex‐ pressed on the lateral and canalicular membranes. There are transporters on the lateral membrane the primary function of which is pumping drugs back into the blood circulation from the hepatocytes. Nowadays, a large amount of work has identified and characterized intestinal and hepatic transporters in regards to tissue expression profiles, regulation, mech‐ anisms of transport, substrate and inhibitor profiles, species differences, and genetic poly‐ morphisms. Given the circumstances outlined above, there is no doubt of the overall

Fruit/Vegetable-Drug Interactions: Effects on Drug Metabolizing Enzymes and Drug Transporters

http://dx.doi.org/10.5772/48283

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Drug metabolizing enzymes and drug transporters play important roles in modulating drug absorption, distribution, metabolism, and elimination. Acting alone or in concert with each other, they can affect the pharmacokinetics and pharmacodynamics of a drug. The interplay between drug metabolizing enzymes and transporters is one of the confounding factors that have been recently shown to contribute to potential complex drug interactions [14].
