Skip to main content
padlock icon - secure page this page is secure

Prioritizing pharmacokinetic drug interaction precipitants in natural products: application to OATP inhibitors in grapefruit juice

Buy Article:

$47.00 + tax (Refund Policy)

Natural products, including botanical dietary supplements and exotic drinks, represent an ever‐increasing share of the health‐care market. The parallel ever‐increasing popularity of self‐medicating with natural products increases the likelihood of co‐consumption with conventional drugs, raising concerns for unwanted natural product–drug interactions. Assessing the drug interaction liability of natural products is challenging due to the complex and variable chemical composition inherent to these products, necessitating a streamlined preclinical testing approach to prioritize precipitant individual constituents for further investigation. Such an approach was evaluated in the current work to prioritize constituents in the model natural product, grapefruit juice, as inhibitors of intestinal organic anion‐transporting peptide (OATP)‐mediated uptake. Using OATP2B1‐expressing MDCKII cells (Madin‐Darby canine kidney type II) and the probe substrate estrone 3‐sulfate, IC50s were determined for constituents representative of the flavanone (naringin, naringenin, hesperidin), furanocoumarin (bergamottin, 6′,7′‐dihydroxybergamottin) and polymethoxyflavone (nobiletin and tangeretin) classes contained in grapefruit juice. Nobiletin was the most potent (IC50, 3.7 μm); 6′,7′‐dihydroxybergamottin, naringin, naringenin and tangeretin were moderately potent (IC50, 20–50 μm); and bergamottin and hesperidin were the least potent (IC50, >300 μm) OATP2B1 inhibitors. Intestinal absorption simulations based on physiochemical properties were used to determine the ratios of unbound concentration to IC50 for each constituent within enterocytes and to prioritize in order of pre‐defined cut‐off values. This streamlined approach could be applied to other natural products that contain multiple precipitants of natural product–drug interactions. Copyright © 2016 John Wiley & Sons, Ltd.
No References
No Citations
No Supplementary Data
No Article Media
No Metrics

Keywords: OATP2B1; drug interaction; grapefruit juice; simulation; transporter

Document Type: Research Article

Publication date: 01 April 2017

  • Access Key
  • Free content
  • Partial Free content
  • New content
  • Open access content
  • Partial Open access content
  • Subscribed content
  • Partial Subscribed content
  • Free trial content
Cookie Policy
X
Cookie Policy
Ingenta Connect website makes use of cookies so as to keep track of data that you have filled in. I am Happy with this Find out more