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Pharmacokinetic interactions and tolerability of berberine chloride with simvastatin and fenofibrate: an open-label, randomized, parallel study in healthy Chinese subjects

Authors Li G, Zhao M, Qiu F, Sun Y, Zhao L

Received 27 August 2018

Accepted for publication 21 November 2018

Published 20 December 2018 Volume 2019:13 Pages 129—139


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 4

Editor who approved publication: Dr Tuo Deng

Guofei Li, Mingming Zhao, Feng Qiu, Yaxin Sun, Limei Zhao

Department of Pharmacy, Shengjing Hospital of China Medical University, Shenyang 110004, China

Purpose: Fenofibrate (Fbt) is a prodrug that has been used to reduce low-density-lipoprotein cholesterol, triglycerides, and increase high-density-lipoprotein cholesterol. Simvastatin (Svt) is a classic lipid-lowering drug that is widely used in the treatment of hypercholesterolemia and hypertriglyceridemia, while berberine chloride (Bbr) is a novel hypolipidemic agent and its blood-lipid-reducing mechanism is distinct from traditional drugs. Currently, drug combination is the trend in treating hyperlipidemia to improve clinical efficacy. The purpose of this study was to evaluate drug interaction from the perspective of pharmacokinetics between Bbr and Fbt/Svt and the tolerability of combined administration in healthy Chinese subjects.
Methods: Healthy subjects (n=60) were randomly allocated to five treatment groups: Bbr alone, Fbt alone, Svt alone, Bbr plus Fbt, and Bbr plus Svt. The experiment was divided into two parts: single-dose administration and multiple-dose administration. Bbr, Fbt, and Svt were taken once every 8 hours, 24 hours, and 24 hours, respectively, over 7 days in the multidose group. Plasma samples were collected and liquid chromatography–mass spectrometry/mass spectrometry was used to detect drug concentrations.
Results: No serious adverse reactions or intolerance were observed throughout the trial. More importantly, the combined-administration groups did not show an increase in incidence of side effects. Coadministration of Fbt and Svt with Bbr had no significant effect on the pharmacokinetic parameters of Bbr, except time to maximum concentration, apparent volume of distribution, and apparent clearance. Concurrent coadministration of Bbr had no obvious impact on the pharmacokinetic behavior of Fbt or Svt. Additionally, there was no significant correlation between sex and pharmacokinetic results.
Conclusion: All treatments were well tolerated. No clinically obvious pharmacokinetic interactions between Bbr and Fbt/Svt were observed with combined administration. The results demonstrated that Bbr can be coadministered safely with Fbt and Svt without dose adjustment.

Keywords: Bbr, Fbt, Svt, drug–drug interaction, pharmacokinetics

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