Studies on Pharmacokinetic Drug Interaction Potential of Vinpocetine

Abstract

BackgroundVinpocetine, 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 the 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).MethodsInhibition 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.ResultsVinpocetine 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.ConclusionStrong 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.

Vinpocetine and Ischemic Stroke

“…VPN is well absorbed from small intestine, which increased by food, therefore, fasting bioavailability is 6.7% and non-fasting bioavailability is 60-100%. Similarly, VPN has no significant drug-drug interactions with different drugs such as oxazepam, imipramine, glibenclamide and other agents that are used in the management of ischemic stroke [6].…”

Role of vinpocetine in ischemic stroke and poststroke outcomes: A critical review

“…Similarly, VPN has no significant drug-drug interactions with different drugs such as oxazepam, imipramine, glibenclamide, and other agents that are used in the management of IS. [6] Vinpocetine in Ischemic Stroke IS represents the main leading cause of death in the United States of America and developed countries and regarded it as the main cause of long-term disability. IS represents 11.9% of annual total death and accounts for 90% of all stroke cases.…”

Inhibitory Effects of Garcinia cambogia Extract on CYP2B6 Enzyme Activity

“…The fold shift in the IC 50 ratio was 1.7. According to a previous report, compounds with a fold shift in the IC 50 ratio of ≥ 1.5 can be considered positive in terms of time-dependent inhibition [13]. Thus, G. cambogia extract may act as a time-dependent inhibitor on CYP2B6 and exhibit an irreversible inhibitory effect on CYP2B6-dependent drug metabolism.…”