A Perspective on Drug-Nutrient Interactions

Boullata, Joseph I.; Barber, Jacqueline R.

doi:10.1007/978-1-59259-781-9_1

Cited by 19 publications

(31 citation statements)

References 101 publications

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“…, saquinavir, atazanavir) (Plosker and Scott, 2003; Le Tiec, 2005). Other examples are discussed comprehensively in several sources (Wolinsky and Williams, 2002; McCabe et al, 2003; Boullata and Armenti, 2004; Meckling, 2007; Stargrove et al, 2008). …”

Section: Underlying Mechanisms Of Food Effect On Drug Exposure Andmentioning

confidence: 99%

“…These biochemical mechanisms, specifically with respect to the intestine, are highlighted in the current review. Examples of other dietary substance-drug interactions are detailed in several sources (Wolinsky and Williams, 2002; McCabe et al, 2003; Boullata & Armenti, 2004; Meckling, 2007; Stargrove et al, 2008). …”

Section: Underlying Mechanisms Of Food Effect On Drug Exposure Andmentioning

confidence: 99%

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Mechanisms underlying food–drug interactions: Inhibition of intestinal metabolism and transport

Won

Oberlies

Paine

2012

Pharmacology & Therapeutics

118

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Food-drug interaction studies are critical to evaluate appropriate dosing, timing, and formulation of new drug candidates. These interactions often reflect prandial-associated changes in the extent and/or rate of systemic drug exposure. Physiologic and physicochemical mechanisms underlying food effects on drug disposition are well-characterized. However, biochemical mechanisms involving drug metabolizing enzymes and transport proteins remain underexplored. Several plant-derived beverages have been shown to modulate enzymes and transporters in the intestine, leading to altered pharmacokinetic (PK) and potentially negative pharmacodynamic (PD) outcomes. Commonly consumed fruit juices, teas, and alcoholic drinks contain phytochemicals that inhibit intestinal cytochrome P450 and phase II conjugation enzymes, as well as uptake and efflux transport proteins. Whereas myriad phytochemicals have been shown to inhibit these processes in vitro, translation to the clinic has been deemed insignificant or undetermined. An overlooked prerequisite for elucidating food effects on drug PK is thorough knowledge of causative bioactive ingredients. Substantial variability in bioactive ingredient composition and activity of a given dietary substance poses a challenge in conducting robust food-drug interaction studies. This confounding factor can be addressed by identifying and characterizing specific components, which could be used as marker compounds to improve clinical trial design and quantitatively predict food effects. Interpretation and integration of data from in vitro, in vivo, and in silico studies require collaborative expertise from multiple disciplines, from botany to clinical pharmacology (i.e., plant to patient). Development of more systematic methods and guidelines is needed to address the general lack of information on examining drug-dietary substance interactions prospectively.

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Section: Underlying Mechanisms Of Food Effect On Drug Exposure Andmentioning

confidence: 99%

Section: Underlying Mechanisms Of Food Effect On Drug Exposure Andmentioning

confidence: 99%

Mechanisms underlying food–drug interactions: Inhibition of intestinal metabolism and transport

Won

Oberlies

Paine

2012

Pharmacology & Therapeutics

118

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“…A drug-dietary substance interaction is defined as the result of a physical, chemical, physiologic, or pathophysiologic relationship between a drug and a nutrient(s) present in a food, nutritional supplement, or food in general [20]. Such an interaction manifests clinically as compromised nutritional status due to addition of a drug or altered pharmacokinetics (PK) and/or pharmacodynamics (PD) of a drug or dietary substance.…”

Section: Overview Of Drug-dietary Substance Interactionsmentioning

confidence: 99%

“…Fruit juices are examples of dietary substances that modify drug metabolism/transport and are the focus of this review. Other examples of drug-dietary substance interactions are discussed comprehensively in several sources [33-36]. …”

Section: Overview Of Drug-dietary Substance Interactionsmentioning

confidence: 99%

Influence of Dietary Substances on Intestinal Drug Metabolism and Transport

Won¹,

Oberlies²,

Paine³

2010

CDM

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Successful delivery of promising new chemical entities via the oral route is rife with challenges, some of which cannot be explained or foreseen during drug development. Further complicating an already multifaceted problem is the obvious, yet often overlooked, effect of dietary substances on drug disposition and response. Some dietary substances, particularly fruit juices, have been shown to inhibit biochemical processes in the intestine, leading to altered pharmacokinetic (PK), and potentially pharmacodynamic (PD), outcomes. Inhibition of intestinal CYP3A-mediated metabolism is the major mechanism by which fruit juices, including grapefruit juice, enhances systemic exposure to new and already marketed drugs. Inhibition of intestinal non-CYP3A enzymes and apically-located transport proteins represent recently identified mechanisms that can alter PK and PD. Several fruit juices have been shown to inhibit these processes in vitro, but some interactions have not translated to the clinic. The lack of in vitro-in vivo concordance is due largely to a lack of rigorous methods to elucidate causative ingredients prior to clinical testing. Identification of specific components and underlying mechanisms is challenging, as dietary substances frequently contain multiple, often unknown, bioactive ingredients that vary in composition and bioactivity. A translational research approach, combining expertise from clinical pharmacologists and natural products chemists, is needed to develop robust models describing PK/PD relationships between a given dietary substance and drug of interest. Validation of these models through well-designed clinical trials would facilitate development of common practice guidelines for managing drug-dietary substance interactions appropriately.

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“…Updates often repeated the same lists of examples without always putting them into clinical or mechanistic perspective. Much of this historic view has been described elsewhere (13). More contemporary reviews and compilations of DNIs have reframed the subject, allowing for a more systematic approach to identifying and evaluating them (14)(15)(16)(17).…”

mentioning

confidence: 98%