title: Is pomegranate juice a potential perpetrator of clinical drug-drug interactions? Review of the in vitro, preclinical and clinical evidence.
abstract: 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.
authors.affiliation: Suramus Biopharm, J. P. Nagar, First Phase, Bangalore, 560078, India, Srini.suramus@yahoo.com.
authors.forename: Nuggehally R
authors.initials: NR
authors.lastname: Srinivas
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000493:pharmacokinetics; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000493:pharmacokinetics; D001189:Aryl Hydrocarbon Hydroxylases / Q000037:antagonists & inhibitors; D001628:Beverages; D002065:Buspirone / Q000493:pharmacokinetics; D018938:Caco-2 Cells; D002121:Calcium Channel Blockers / Q000493:pharmacokinetics; D002220:Carbamazepine / Q000493:pharmacokinetics; D065729:Cytochrome P-450 CYP2C9; D051544:Cytochrome P-450 CYP3A; D065692:Cytochrome P-450 CYP3A Inhibitors; D004353:Drug Evaluation, Preclinical; D004347:Drug Interactions; D005480:Flurbiprofen / Q000493:pharmacokinetics; D018565:Food-Drug Interactions; D006801:Humans; D006993:Hypnotics and Sedatives / Q000493:pharmacokinetics; D007004:Hypoglycemic Agents / Q000493:pharmacokinetics; D029561:Lythraceae / Q000737:chemistry*; D008874:Midazolam / Q000493:pharmacokinetics; D009568:Nitrendipine / Q000493:pharmacokinetics; D014044:Tolbutamide / Q000493:pharmacokinetics; D014229:Triazolam / Q000493:pharmacokinetics
chemical_list: D014151:Anti-Anxiety Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D002121:Calcium Channel Blockers; D065692:Cytochrome P-450 CYP3A Inhibitors; D006993:Hypnotics and Sedatives; D007004:Hypoglycemic Agents; D014229:Triazolam; D002220:Carbamazepine; D005480:Flurbiprofen; D014044:Tolbutamide; D009568:Nitrendipine; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D008874:Midazolam; D002065:Buspirone