Effect of Natural Phenolics on Pharmacokinetic Modulation of Bedaquiline in Rat to Assess the Likelihood of Potential Food–Drug Interaction

• DOI: 10.1021/acs.jafc.9b06529
• Publication Date: 2020-01-13T11:15:07Z
• Authors: Pankul Kotwal; Ashish Dogra; Ankita Sharma; Shipra Bhatt; Abhishek Gour; Sumit Sharma; Priya Wazir; Parvinder Pal Singh; Ajay Kumar; Utpal Nandi
• Keywords: Bedaquiline; Natural product; Phytochemical

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