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Cranberry Ingestion Modulated Drug Transporters and Metabolizing Enzymes: Gefitinib Used as a Probe Substrate in Rats

Chung-Ping Yu1,2, Pei-Ling Tsai1, Pei-Ying Li1

  • 1School of Pharmacy, College of Pharmacy, China Medical University, Taichung 406040, Taiwan.

Molecules (Basel, Switzerland)
|September 23, 2022
PubMed

Insights

Cranberry juice significantly alters the absorption and metabolism of the cancer drug gefitinib by affecting key drug transporters and enzymes in the body. This interaction impacts how the body processes gefitinib.

Area of Science:

  • Pharmacology
  • Nutritional Science
  • Drug Metabolism

Background:

  • Cranberry is a polyphenol-rich food used for urinary tract infection prevention.
  • Gefitinib, an anticancer drug, is processed by P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), and cytochrome P450 enzymes (CYP3A4, CYP2D6).

Purpose of the Study:

  • To investigate how cranberry juice affects the drug transporters P-gp and BCRP.
  • To examine the impact of cranberry on the metabolic enzymes CYP3A4 and CYP2D6 using gefitinib as a probe substrate.

Main Methods:

  • Rats were given gefitinib with or without cranberry juice (5.0 g/kg).
  • Serum gefitinib concentrations were measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS).
  • Changes in protein levels of P-gp, BCRP, CYP3A4, and CYP2D6 in enterocytes and hepatocytes were analyzed.

Main Results:

  • Cranberry juice significantly increased gefitinib's maximum concentration (Cmax) by 28% and area under the curve (AUC0-t) by 55%.
  • Cranberry juice activated P-gp and its metabolites inhibited CYP2D6.
  • Protein levels of P-gp, BCRP, CYP3A4, and CYP2D6 were altered in rat enterocytes and hepatocytes.

Conclusions:

  • Cranberry juice consumption influences the activity and protein expression of critical drug transporters and metabolizing enzymes.
  • These findings highlight potential drug-food interactions between cranberry and gefitinib, impacting gefitinib's efficacy and safety.
Keywords:
cranberrycytochrome P450sdrug transportergefitinibpharmacokinetics

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