Effect of Natural Phenolics on Pharmacokinetic Modulation of Bedaquiline in Rat to Assess the Likelihood of Potential Food-Drug Interaction.,Journal of Agricultural and Food Chemistry

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Effect of Natural Phenolics on Pharmacokinetic Modulation of Bedaquiline in Rat to Assess the Likelihood of Potential Food-Drug Interaction.
Journal of Agricultural and Food Chemistry ( IF 5.7 ) Pub Date : 2020-01-13 , DOI: 10.1021/acs.jafc.9b06529
Pankul Kotwal _{1,

2} , Ashish Dogra _{1,

2} , Ankita Sharma _{1,

2} , Shipra Bhatt _{1,

2} , Abhishek Gour _{1,

2} , Sumit Sharma _{2,

3} , Priya Wazir ₁ , Parvinder Pal Singh _{2,

3} , Ajay Kumar _{1,

2} , Utpal Nandi _{1,

2}

Affiliation

Bedaquiline (TMC-207) is a recently approved drug for the treatment of multidrug-resistant tuberculosis (MDR-TB). Moreover, there is a present and growing concern for natural-product-mediated drug interaction, as these are inadvertently taken by patients as a dietary supplement, food additive, and medicine. In the present study, we investigated the impact of 20 plant-based natural products, typically phenolics, on in vivo oral bedaquiline pharmacokinetics, as previous studies are lacking. Three natural phenolics were identified that can significantly enhance the oral exposure of bedaquiline upon coadministration. We further investigated the possible role of all of the phytochemicals on in vitro P-glycoprotein (P-gp) induction and inhibition and CYP3A4 inhibition in a single platform as bedaquiline is the substrate for both P-gp and CYP3A4. In conclusion, curcumin, CC-I (3',5-dihydroxyflavone-7-O-β-d-galacturonide-4'-O-β-d-glucopyranoside), and 6-gingerol should not be coadministered with bedaquiline to avoid untoward drug interactions and, subsequently, its dose-dependent adverse effects.

中文翻译：

天然酚对大鼠贝达喹啉药代动力学调节的作用，以评估潜在的食物-药物相互作用的可能性。

Bedaquiline（TMC-207）是最近被批准用于治疗耐多药结核病（MDR-TB）的药物。此外，由于天然产物介导的药物相互作用被患者不经意地用作饮食补充剂，食品添加剂和药物，因此，目前存在并且日益引起人们的关注。在本研究中，由于缺乏先前的研究，我们调查了20种基于植物的天然产物（通常为酚类）对体内口服苯达喹啉药代动力学的影响。鉴定出三种天然酚类药物，它们可以在共同给药时显着提高苯达喹啉的口服暴露量。我们进一步研究了所有植物化学物质在体外平台上对P-糖蛋白（P-gp）的诱导和抑制以及对CYP3A4抑制的可能作用，因为苯达喹啉是P-gp和CYP3A4的底物。

更新日期：2020-01-26

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