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Molecules 2016, 21(4), 464; doi:10.3390/molecules21040464

In Vivo and in Vitro Study on Drug-Drug Interaction of Lovastatin and Berberine from Pharmacokinetic and HepG2 Cell Metabolism Studies

1
Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
2
College of Pharmacy, Shannxi University of Traditional Chinese Medicine, Xianyang 712046, China
3
College of Pharmacy, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China
4
Department of Agriculture and Life Sciences, Ankang University, Ankang 725000, China
*
Authors to whom correspondence should be addressed.
Academic Editor: Arduino Mangoni
Received: 18 February 2016 / Revised: 18 March 2016 / Accepted: 30 March 2016 / Published: 8 April 2016
(This article belongs to the Section Metabolites)
View Full-Text   |   Download PDF [849 KB, uploaded 8 April 2016]   |  

Abstract

Background: We assumed that the pharmacokinetics of lovastatin could be changed by the induction effect of berberine. Methods: An UPLC-MS/MS method was developed and validated for the pharmacokinetics tudy of lovastatin to investigate the in vivo drug-drug interactions between lovastatin and berberine. SD male rats were random divided into lovastatin group and berberine induced prior to lovastatin group for the in vivo pharmacokinetic studies. Meanwhile HepG2 cells were induced by berberine for three days to study the metabolism of lovastatin. Results: The AUC (p < 0.01) and Cmax (p < 0.01) could be significantly decreased in the berberine-induced group in vivo, and the metabolic activity of HepG2 cell ccould be increased by berberine induction in vitro. The metabolism parameters of lovastatin such as CL, Vmax and Km were increased after the induction of berberine. From the pharmacokinetic study of lovastatin induced with berberine, we obtained pharmacokinetic parameters which are compliance with the metabolic parameters of lovastatin in HepG2 cells with berberine induction in vitro. Conclusions: From the in vivo pharmacokinetics study and the HepG2 cell metabolism study in vitro, berberine could be an inducer for the metabolism of lovastatin according to our previous research on berberine induction effects on HepG2 cells, which may be relevant to the fact that berberine possesses induction effects through the CYP 450 3A4 enzyme. View Full-Text
Keywords: in vivo and in vitro; berberine; lovastatin; pharmacokinetics; HepG2 cell in vivo and in vitro; berberine; lovastatin; pharmacokinetics; HepG2 cell
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MDPI and ACS Style

Cui, H.; Wang, J.; Zhang, Q.; Dang, M.; Liu, H.; Dong, Y.; Zhang, L.; Yang, F.; Wu, J.; Tong, X. In Vivo and in Vitro Study on Drug-Drug Interaction of Lovastatin and Berberine from Pharmacokinetic and HepG2 Cell Metabolism Studies. Molecules 2016, 21, 464.

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