Mechanisms underlying food-drug interactions: inhibition of intestinal metabolism and transport.
Mechanisms underlying food-drug interactions: inhibition of intestinal metabolism and transport.
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DOI：
10.1016/j.pharmthera.2012.08.001
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发表时间：
2012-11
影响因子：
13.5
通讯作者：
Paine, Mary F.
中科院分区：
文献类型：
--
作者：
Won, Christina S.;Oberlies, Nicholas H.;Paine, Mary F.
食物-药物相互作用研究对于评估新候选药物的适当剂量、时机和配方至关重要。这些相互作用通常反映了与膳食相关的全身药物暴露程度和/或速率的变化。食物对药物处置影响的生理和物理化学机制已得到充分表征。然而，涉及药物代谢酶和转运蛋白的生化机制仍未得到充分探索。几种植物源饮料已被证明可以调节肠道内的酶和转运蛋白，从而导致药代动力学 (PK) 改变和潜在的负面药效 (PD) 结果。常用的果汁、茶和酒精饮料含有抑制肠道细胞色素 P450 和 II 相结合酶以及摄取和流出转运蛋白的植物化学物质。尽管无数植物化学物质已被证明可以在体外抑制这些过程，但临床转化被认为是微不足道或不确定的。阐明食物对药物 PK 影响的一个被忽视的先决条件是对致病生物活性成分的全面了解。特定膳食物质的生物活性成分组成和活性的显着变化对进行稳健的食物-药物相互作用研究提出了挑战。这种混杂因素可以通过识别和表征特定成分来解决，这些成分可以用作标记化合物来改进临床试验设计并定量预测食物影响。体外、体内和计算机研究数据的解释和整合需要来自多个学科的协作专业知识，从植物学到临床药理学（即从植物到患者）。需要制定更系统的方法和指南，以解决前瞻性检查药物-膳食物质相互作用信息普遍缺乏的问题。
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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影响因子：
3.2
作者：
Antonello, Michele;Montemurro, Domenico;Rossi, Gian Paolo
通讯作者：
Rossi, Gian Paolo
影响因子：
4.5
作者：
Bolger, Michael B.;Lukacova, Viera;Woltosz, Walter S.
通讯作者：
Woltosz, Walter S.
DOI：
10.1515/dmdi.2011.031
发表时间：
2011-12-01
期刊：
Drug Metabolism and Drug Interactions
影响因子：
--
作者：
Boulenc, Xavier;Barberan, Olivier
通讯作者：
Barberan, Olivier
影响因子：
3.4
作者：
Bailey, David G.
通讯作者：
Bailey, David G.
影响因子：
4.9
作者：
Benet LZ
通讯作者：
Benet LZ