title: Pomegranate juice does not affect the disposition of simvastatin in healthy subjects.
abstract: Previous in vitro and in vivo investigations reported controversial results for the inhibitory potential of pomegranate on Cytochrome P450 (CYP) 3A activity. This study evaluated the effect of pomegranate juice on the disposition of simvastatin, a CYP3A4 substrate, and simvastatin acid, its active metabolite, compared with grapefruit juice in healthy subjects. A single oral pharmacokinetic study of 40 mg simvastatin was conducted as a three-way crossover (control, pomegranate, and grapefruit juices) in 12 healthy male subjects. The subjects took pomegranate or grapefruit juice three times per day for 3 days (900 mL/day) and on the third day, the pharmacokinetic study was executed. Blood samples were collected to 24 h post-dose and the pharmacokinetic parameters of simvastatin and simvastatin acid were compared among the study periods. In the period of grapefruit juice, the mean C max and AUCinf of simvastatin [the geometric mean ratio (90 % CI) 15.6 (11.6-21.0) and 9.1 (6.0-13.7)] were increased significantly when compared with the control period, whereas they were not significantly different in the period of pomegranate juice [C max and AUCinf 1.20 (0.89-1.62) and 1.29 (0.85-1.94)]. The mean C max and AUCinf of simvastatin acid were increased significantly after intake of grapefruit juice, but not pomegranate juice. These results suggest that pomegranate juice affects little on the disposition of simvastatin in humans. Pomegranate juice does not seem to have a clinically relevant inhibitory potential on CYP3A4 activity.
authors.affiliation: Department of Anatomy and Histology, College of Oriental Medicine, Daegu Haany University, Gyeongsan, Korea.
authors.forename: Soo-Jin
authors.initials: SJ
authors.lastname: Park
authors.affiliation: Department of Pharmacology and PharmacoGenomics Research Center, Inje University College of Medicine, Busan, Korea.|Department of Clinical Pharmacology, Busan Paik Hospital, Busan, Korea.
authors.forename: Chang-Woo
authors.initials: CW
authors.lastname: Yeo
authors.affiliation: Department of Pharmacology and PharmacoGenomics Research Center, Inje University College of Medicine, Busan, Korea.|Department of Clinical Pharmacology, Busan Paik Hospital, Busan, Korea.
authors.forename: Eon-Jeong
authors.initials: EJ
authors.lastname: Shim
authors.affiliation: Herbal Medicine Research Division, Pharmaceutical and Medical Device Research Department, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety, Cheongwon, Korea.
authors.forename: Hyunmi
authors.initials: H
authors.lastname: Kim
authors.affiliation: College of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu, Korea.
authors.forename: Kwang-Hyeon
authors.initials: KH
authors.lastname: Liu
authors.affiliation: Department of Pharmacology and PharmacoGenomics Research Center, Inje University College of Medicine, Busan, Korea. phshinjg@inje.ac.kr.|Department of Clinical Pharmacology, Busan Paik Hospital, Busan, Korea. phshinjg@inje.ac.kr.
authors.forename: Jae-Gook
authors.initials: JG
authors.lastname: Shin
authors.affiliation: Department of Pharmacology and PharmacoGenomics Research Center, Inje University College of Medicine, Busan, Korea. phshon@gmail.com.|Department of Clinical Pharmacology, Busan Paik Hospital, Busan, Korea. phshon@gmail.com.
authors.forename: Ji-Hong
authors.initials: JH
authors.lastname: Shon
mesh_terms: D000328:Adult; D019540:Area Under Curve; D001628:Beverages / Q000009:adverse effects; D032083:Citrus paradisi / Q000009:adverse effects; D018592:Cross-Over Studies; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism; D018565:Food-Drug Interactions; D000067030:Fruit and Vegetable Juices / Q000009:adverse effects*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000493:pharmacokinetics*; D029561:Lythraceae / Q000009:adverse effects*; D008297:Male; D019821:Simvastatin / Q000493:pharmacokinetics*; D055815:Young Adult
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D019821:Simvastatin; D051544:Cytochrome P-450 CYP3A
keywords: CYP3A; Drug interactions; Grapefruit juice; Pomegranate; Simvastatin