Journal article
Mechanisms underlying food-drug interactions: inhibition of intestinal metabolism and transport
Pharmacology & therapeutics (Oxford), Vol.136(2), pp.186-201
11/2012
Handle:
https://hdl.handle.net/2376/108152
PMCID: PMC3466398
PMID: 22884524
Abstract
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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Details
- Title
- Mechanisms underlying food-drug interactions: inhibition of intestinal metabolism and transport
- Creators
- Christina S Won - Division of Pharmacotherapy and Experimental Therapeutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7569, USANicholas H OberliesMary F Paine
- Publication Details
- Pharmacology & therapeutics (Oxford), Vol.136(2), pp.186-201
- Academic Unit
- Pharmaceutical Sciences, Department of
- Publisher
- England
- Grant note
- R01 GM077482 / NIGMS NIH HHS
- Identifiers
- 99900547145301842
- Language
- English
- Resource Type
- Journal article