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Effects of Verapamil on the Pharmacokinetics of Dihydromyricetin in Rats and Its Potential Mechanism

Effects of Verapamil on the Pharmacokinetics of Dihydromyricetin in Rats and Its Potential Mechanism

Yixiang Huang, Junyong Zhao, Wei Jian, Gang Wang

Xenobiotica. 2018 Aug;48(8):839-844.

PMID: 28795912

Abstract:

1. This study investigates the effects of verapamil on the pharmacokinetics of dihydromyricetin in rats and clarifies its main mechanism. 2. The pharmacokinetic profiles of oral or intravenous administration of dihydromyricetin in Sprague-Dawley rats with or without pretreatment with verapamil were investigated. In addition, the effects of verapamil on the transport and metabolic stability of dihydromyricetin were investigated using Caco-2 cell transwell model and rat liver microsomes. 3. In the oral group, verapamil could significantly increase Cmax, and decrease oral clearance of dihydromyricetin (p < 0.05). In the intravenous group, the Cmax also increased compared with the control group, but the difference was not significant. However, the t1/2 and clearance rate decreased than that of the control (p < 0.05). The oral bioavailability increased significantly (p < 0.05) from 3.84% to 6.84% with the pretreatment of verapamil. A markedly higher transport of dihydromyricetin across the Caco-2 cells was observed in the basolateral-to-apical direction and was abrogated in the presence of the P-gp inhibitor, verapamil. Additionally, the intrinsic clearance rate of dihydromyricetin was decreased by the pretreatment with verapamil (27.0 versus 32.5 μL/min/mg protein). 4. Those results indicated that verapamil could significantly change the pharmacokinetic profiles of dihydromyricetin in rats, and it might exert these effects through increasing the absorption of dihydromyricetin by inhibiting the activity of P-gp, or through inhibiting the metabolism of dihydromyricetin in rat liver.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP27200120	Dihydromyricetin		27200-12-0	Price

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