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Pomegranate juice does not affect the disposition of simvastatin in healthy subjects

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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.

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Acknowledgments

The authors have no conflict of interest to report. This work was supported by the National Research Foundation of Korea grant funded by the Korea government (No. R13-2007-023-00000-0). We thank Charles Lund for giving a help for English writing.

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Authors and Affiliations

  1. Department of Anatomy and Histology, College of Oriental Medicine, Daegu Haany University, Gyeongsan, Korea

    Soo-Jin Park

  2. Department of Pharmacology and PharmacoGenomics Research Center, Inje University College of Medicine, Busan, Korea

    Chang-Woo Yeo, Eon-Jeong Shim, Jae-Gook Shin & Ji-Hong Shon

  3. Department of Clinical Pharmacology, Busan Paik Hospital, Busan, Korea

    Chang-Woo Yeo, Eon-Jeong Shim, Jae-Gook Shin & Ji-Hong Shon

  4. 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

    Hyunmi Kim

  5. College of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu, Korea

    Kwang-Hyeon Liu

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  1. Soo-Jin Park
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  2. Chang-Woo Yeo
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Correspondence to Jae-Gook Shin or Ji-Hong Shon.

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Park, SJ., Yeo, CW., Shim, EJ. et al. Pomegranate juice does not affect the disposition of simvastatin in healthy subjects. Eur J Drug Metab Pharmacokinet 41, 339–344 (2016). https://doi.org/10.1007/s13318-015-0263-8

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  • DOI: https://doi.org/10.1007/s13318-015-0263-8

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