**3. Food and drug transporters**

The oral administration of drugs to patients is convenient, practical, and preferred for many reasons. Oral administration of drugs, however, may lead to limited and variable oral bioa‐ vailability because of absorption across the intestinal barrier [15,16]. Drug absorption across the gastrointestinal tract is highly dependent on affinity for membrane transporters as well as lipophilicity [17]. On the other hand, the liver plays a key role in the clearance and excre‐ tion of many drugs. Hepatic transporters are membrane proteins that primarily facilitate nu‐ trient and endogenous substrate transport into the cell via uptake transporters, or protect the cell by pumping out toxic chemicals via canalicular transporters [18]. Consequently, drug transporters in both the gut and the liver are important in determining oral drug dis‐ position by controlling absorption and bioavailability [19]

The major uptake transporters responsible for nutrient and xenobiotic transport, both up‐ take and efflux transporters, belong to the two solute carrier (SLC and SLCO) superfamilies [20]. The SLC superfamily encompasses a variety of transporters, including the organic anion transporters (OAT, SLC22A), the organic cation transporters (OCT, SLC22A), the elec‐ troneutral organic cation transporters (OCTN, SLC22A), the equilibrative nucleoside trans‐ porters (ENT, SLC29), the concentrative nucleoside transporters (CNT, SLC28), the apical Na+ −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 relevance of drug transport for clinical pharmacokinetics.

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.
