Is pomegranate juice a potential perpetrator of clinical drug-drug interactions? Review of the in vitro, preclinical and clinical evidence

Eur J Drug Metab Pharmacokinet. 2013 Dec;38(4):223-9. doi: 10.1007/s13318-013-0137-x. Epub 2013 May 15.


The area of fruit juice-drug interaction has received wide attention with numerous scientific and clinical investigations performed and reported for scores of drugs metabolized by CYP3A4/CYP2C9. While grapefruit juice has been extensively studied with respect to its drug-drug interaction potential, numerous other fruit juices such as cranberry juice, orange juice, grape juice, pineapple juice and pomegranate juice have also been investigated for its potential to show drug-drug interaction of any clinical relevance. This review focuses on establishing any relevance for clinical drug-drug interaction potential with pomegranate juice, which has been shown to produce therapeutic benefits over a wide range of disease areas. The review collates and evaluates relevant published in vitro, preclinical and clinical evidence of the potential of pomegranate juice to be a perpetrator in drug-drug interactions mediated by CYP3A4 and CYP2C9. In vitro and animal pharmacokinetic data support the possibility of CYP3A4/CYP2C9 inhibition by pomegranate juice; however, the human relevance for drug-drug interaction was not established based on the limited case studies.

MeSH terms

  • Animals
  • Anti-Anxiety Agents / pharmacokinetics
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacokinetics
  • Aryl Hydrocarbon Hydroxylases / antagonists & inhibitors
  • Beverages*
  • Buspirone / pharmacokinetics
  • Caco-2 Cells
  • Calcium Channel Blockers / pharmacokinetics
  • Carbamazepine / pharmacokinetics
  • Cytochrome P-450 CYP2C9
  • Cytochrome P-450 CYP3A
  • Cytochrome P-450 CYP3A Inhibitors
  • Drug Evaluation, Preclinical
  • Drug Interactions*
  • Flurbiprofen / pharmacokinetics
  • Food-Drug Interactions*
  • Humans
  • Hypnotics and Sedatives / pharmacokinetics
  • Hypoglycemic Agents / pharmacokinetics
  • Lythraceae / chemistry*
  • Midazolam / pharmacokinetics
  • Nitrendipine / pharmacokinetics
  • Tolbutamide / pharmacokinetics
  • Triazolam / pharmacokinetics


  • Anti-Anxiety Agents
  • Anti-Inflammatory Agents, Non-Steroidal
  • Calcium Channel Blockers
  • Cytochrome P-450 CYP3A Inhibitors
  • Hypnotics and Sedatives
  • Hypoglycemic Agents
  • Triazolam
  • Carbamazepine
  • Flurbiprofen
  • Tolbutamide
  • Nitrendipine
  • CYP2C9 protein, human
  • Cytochrome P-450 CYP2C9
  • Aryl Hydrocarbon Hydroxylases
  • Cytochrome P-450 CYP3A
  • CYP3A4 protein, human
  • Midazolam
  • Buspirone