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The Pregnane X Receptor Agonist St John’s Wort Has No Effects on the Pharmacokinetics and Pharmacodynamics of Repaglinide

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Abstract

Background and Objectives: St John’s wort (SJW; Hypericum perforatum) has been one of the most commonly used herbal remedies for mood disorders. This study aimed to investigate the effect of SJW, a pregnane X receptor (PXR) agonist, on the pharmacokinetics and pharmacodynamics of repaglinide, a widely consumed glucose-lowering drug.

Methods: In a two-phase, randomized, crossover study with a 4-week washout period between phases, 15 healthy subjects with specific solute carrier organic anion transporter family member 1B1 (SLCO1B1) genotypes were given pretreatment with SJW 325 mg or placebo three times daily for 14 days, and a single dose of repaglinide 1mg was administered followed by 75 g glucose at 15 minutes after repaglinide administration.

Results: In all subjects, SJW had no effect on the total area under the plasma concentration-time curve from time zero to infinity (AUC∞), the peak plasma concentration (Cmax) or the elimination half-life (t½) of repaglinide. In addition, SJW had no significant effect on the blood glucose-lowering and insulin-elevating effects of repaglinide.

Conclusion: Consumption of SJW for 14 days had no clinically significant effect on the pharmacokinetics and pharmacodynamics of repaglinide.

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Acknowledgements

This work was supported by research grants from the National Scientific Foundation of China (grant nos. 30801421, 30901834 and 30873089), Huge Project to Boost Chinese Drug Development (grant nos. 2009ZX09501-032 and 2009ZX09304-003), 863 Project (grant nos. 2009AA022710, 2009AA022703 and 2009AA022704), Fundamental Research Funds for the Central Universities (grant nos. 2010QZZD010 and 201023100001), Program for Changjiang Scholars and Innovative Research Team in University (grant no. IRT0946) and State Key Laboratory of Drug Research (grant no. SIMM0812KF-01). The authors have no conflicts of interest that are directly relevant to the content of this study.

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  1. Hunan Key Laboratory of Pharmacogenetics, Pharmacogenetics Research Institute, Institute of Clinical Pharmacology, Central South University, Changsha, Hunan, 410078, P. R. China

    Lan Fan, Gan Zhou, Dong Guo, Ya-Li Liu, Wang-Qing Chen, Zhao-Qian Liu, Zhi-Rong Tan, Deng Sheng, Hong-Hao Zhou &  Wei Zhang

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  1. Lan Fan
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Fan, L., Zhou, G., Guo, D. et al. The Pregnane X Receptor Agonist St John’s Wort Has No Effects on the Pharmacokinetics and Pharmacodynamics of Repaglinide. Clin Pharmacokinet 50, 605–611 (2011). https://doi.org/10.2165/11587310-000000000-00000

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  • DOI: https://doi.org/10.2165/11587310-000000000-00000

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