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ARS Home » Southeast Area » Oxford, Mississippi » Natural Products Utilization Research » Research » Publications at this Location » Publication #318907
Title: Studies on pharmacokinetic drug interaction potential of vinpocetine

Author
item MANDA, VAMSHI - University Of Mississippi
item AVULA, BHARATHI - University Of Mississippi
item DALE, OLIVIA - University Of Mississippi
item CHITTIBOYINA, AMAR - University Of Mississippi
item KHAN, IKHLAS - University Of Mississippi
item WALKER, LARRY - University Of Mississippi
item KHAN, SHABANA - University Of Mississippi

Submitted to: Medicines (ISSN 2305-6320)
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/2/2015
Publication Date: 6/5/2015
Publication URL: http://handle.nal.usda.gov/10113/62598
Citation: Manda, V.K., Avula, B., Dale, O.R., Chittiboyina, A.G., Khan, I.A., Walker, L.A., Khan, S.I. 2015. Studies on pharmacokinetic drug interaction potential of vinpocetine. Medicines (ISSN 2305-6320). 2:93-105. doi:10.3390/medicines2020093

Interpretive Summary: Vinpocetine is a semi-synthetic derivative of a natural alkaloid vincamine, present in the leaves of Vinca minor (lesser periwinkle) plant. In the US and rest of the countries, it is sold as a dietary supplement and is also a component of many products with muscle building and weight-loss claims. Commercially, it is primarily marketed as a neuroprotective and memory-enhancing supplement. Our current study was focused on identifying the risk of vinpocetine to cause any interactions with drugs that are taken in combination.

Technical Abstract: Background: Vinpocetine, a semi-synthetic derivative of vincamine, is a popular dietary supplement used for the treatment of several central nervous system related disorders. Despite its wide use, no pharmacokinetic drug interaction studies are reported in literature. Due to increasing use of dietary supplements in combination with conventional drugs, the risk of adverse effects is on the rise. As a preliminary step to predict a possibility of drug interaction during concomitant use of vinpocetine and conventional drugs, this study was carried out to evaluate the effects of vinpocetine on three main regulators of pharmacokinetic drug interactions namely, cytochromes P450 (CYPs), P-glycoprotein (P-gp), and Pregnane X receptor (PXR). Methods: Inhibition of CYPs was evaluated by employing recombinant enzymes. The inhibition of P-gp was determined by calcein-AM uptake method in transfected and wild type MDCKII cells. Modulation of PXR activity was monitored through a reporter gene assay in HepG2 cells. Results: Vinpocetine showed a strong inhibition of P-gp (EC50 8 µM) and a moderate inhibition of recombinant CYP3A4 and CYP2D6 (IC50 2.8 and 6.5 µM) with no activity towards CYP2C9, CYP2C19 and CYP1A2 enzymes. In HLM, competitive inhibition of CYP3A4 (IC50 54 and Ki 19 µM) and non-competitive inhibition of CYP2D6 (IC50 19 and Ki 26 µM) was observed. Activation of PXR was observed only at the highest tested concentration of vinpocetine (30 µM) while lower doses were ineffective. Conclusion: Strong inhibition of P-gp by vinpocetine is indicative of a possibility of drug interactions by altering the pharmacokinetics of drugs which are the substrates of P-gp. However the effects on CYPs and PXR indicate that vinpocetine may not affect CYP-mediated metabolism of drugs as the inhibitory concentrations are much greater than the expected plasma concentrations in humans.