The Effect of Vinpocetine on Human Cytochrome P450 Isoenzymes by Using a Cocktail Method.

Lingti Kong,Meiling Yu,Chunli Song,Rong Xing,Daohua Guo,Linhu Ye

doi:10.1155/2016/5017135

Abstract

Vinpocetine is a derivative of the alkaloid vincamine, which had been prescribed for chronic cerebral vascular ischemia and acute ischemic stroke or used as a dietary supplement for its several different mechanisms of biological activities. However, information on the cytochrome P450 (CYP) enzyme-mediated drug metabolism has not been previously studied. The present study was performed to investigate the effects of vinpocetine on CYPs activity, and cocktail method was used, respectively. To evaluate the effects of vinpocetine on the activity of human CYP3A4, CYP2C9, CYP2C19, CYP2D6, and CYP2E1, human liver microsomes were utilized to incubate with the mixed CYPs probe substrates and the target components. The results indicate that vinpocetine exhibited weak inhibitory effect on the CYP2C9, where the IC50 value is 68.96 μM, whereas the IC50 values for CYP3A4, CYP2C19, CYP2D6, and CYP2E1 were all over range of 100 μM, which showed that vinpocetine had no apparent inhibitory effects on these CYPs. In conclusion, the results indicated that drugs metabolized by CYP2C9 coadministrated with vinpocetine may require attention or dose adjustment.

Highlights

Vinpocetine, ethyl (3α,16α)-eburnamenine-14-carboxylate (Figure 1), which is a derivative of the alkaloid vincamine had found several different mechanisms of biological activities, including neuroprotective [1], anti-inflammatory [2, 3], antinociceptive [4], and antiseizure activities [5]
Vinpocetine is primarily prescribed for chronic cerebral vascular ischemia and acute ischemic stroke in China, Germany, Japan, Hungary, Poland, Russia, and other countries [6]
More than 300 brands of dietary supplements, which are regulated as food and sold directly to consumers, labelled as containing vinpocetine, are available for sale in the United States [7]

Summary

Introduction

Vinpocetine, ethyl (3α,16α)-eburnamenine-14-carboxylate (Figure 1), which is a derivative of the alkaloid vincamine had found several different mechanisms of biological activities, including neuroprotective [1], anti-inflammatory [2, 3], antinociceptive [4], and antiseizure activities [5]. More than 300 brands of dietary supplements, which are regulated as food and sold directly to consumers, labelled as containing vinpocetine, are available for sale in the United States [7]. Vinpocetine has displayed adverse effects including conditions such as facial flushing, headaches, and drop of blood pressure [7]. Vinpocetine readily enters the bloodstream from the stomach and gastrointestinal tract and passes the blood-brain barrier. Vinpocetine was metabolized exclusively in the liver of dogs and humans, whereas in rats extrahepatic metabolism seems to be important [8, 9]; apovincaminic acid is the main hydrolysis metabolite of vinpocetine and is eliminated from the body through the kidneys [10]

Objectives

Methods

Results