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Pharmacokinetics of Hesperetin and Naringenin in the Zhi Zhu Wan, a Traditional Chinese Medicinal Formulae, and its Pharmacodynamics Study

2012; Wiley; Volume: 27; Issue: 9 Linguagem: Inglês

10.1002/ptr.4867

1099-1573

Hui Sun, Tianwei Dong, Aihua Zhang, Jinfeng Yang, Guangli Yan, Tetsuro Sakurai, Xiuhong Wu, Ying Han, Xijun Wang,

Chromatography in Natural Products

Zhi Zhu Wan (ZZW), a classical Chinese medical formulae consisted of Atractylodes Rhizome and Fructus Citrus Immaturus , has been commonly used for treatment of gastrointestinal diseases. Hesperetin and naringenin are the main components of ZZW, and both can alleviate intestinal tract disorders. In this work, plasma pharmacokinetics and pharmacodynamics characteristics of ZZW after oral administration were investigated using a rapid and sensitive ultra performance liquid chromatography–tandem mass spectrometry method with an electrospray ionization source in positive ion mode. Biosamples were prepared using methanolic precipitation, and the separation of hesperetin and naringenin was achieved on a Waters ACQUITY HSS BEH (2.1 mm × 5 mm, 1.7 µm) column by linear gradient elution, and the total run time was only 3 min. Data were analyzed and estimated using WinNonlin Professional version 5.1. With pharmacokinetic analysis, the estimated pharmacokinetic parameters (i.e. C max , area under the concentration–time curve (AUC) and t 1/2 ), were C max = 776.06 ng/mL, AUC = 9473 ng/mL·h, t1/2 = 5.26 h for hesperetin and C max = 2910.6 ng/mL, AUC = 40607.9 ng/mL·h, t1/2 = 4.69 h for naringenin, respectively. In the present study, we have also valuated and clarified the effect of ZZW on small intestinal movement. It was found that ZZW can accelerate intestinal motility in mice and may hold a promising treatment for intestinal diseases. Copyright © 2012 John Wiley & Sons, Ltd.