Planta Medica International Open 2017; 4(S 01): S1-S202
DOI: 10.1055/s-0037-1608573
Lecture Session – Miscellaneous
Georg Thieme Verlag KG Stuttgart · New York

STABILITY AND INTESTINAL ABSORPTION OF VINPOCETINE IN HUMAN EPITHELIAL CACO-2 CELLS

S Piazza
1   Department of Pharmacological and Biomolecular Sciences University of Milan, Milan, Italy
,
E Sangiovanni
1   Department of Pharmacological and Biomolecular Sciences University of Milan, Milan, Italy
,
M Maldini
1   Department of Pharmacological and Biomolecular Sciences University of Milan, Milan, Italy
,
M Fumagalli
1   Department of Pharmacological and Biomolecular Sciences University of Milan, Milan, Italy
,
R Spezzano
1   Department of Pharmacological and Biomolecular Sciences University of Milan, Milan, Italy
,
F Giavarini
1   Department of Pharmacological and Biomolecular Sciences University of Milan, Milan, Italy
,
B Pacchetti
2   Linnea SA, Riazzino, Switzerland
,
D Caruso
1   Department of Pharmacological and Biomolecular Sciences University of Milan, Milan, Italy
,
M Dell'Agli
1   Department of Pharmacological and Biomolecular Sciences University of Milan, Milan, Italy
› Author Affiliations
Further Information

Publication History

Publication Date:
24 October 2017 (online)

 

The semi-synthetic alkaloid vinpocetine is widely used in Europe and Japan for the improvement of neurodegenerative diseases1. The compound is insoluble in water and slightly absorbed mainly by small intestine. Vinpocetine undergoes extensive metabolism into its hydrolysis product apovincaminic acid2. The poor bioavailability is only partially explained, since the effect of the intestinal digestive process on its stability has never been previously investigated.

The aim of the present study was to evaluate the stability and absorption of vinpocetine in human Caco-2 cells, before and after an in vitro simulated intestinal digestion.

The intestinal absorption of 50 mM (17.52 ng/mL) vinpocetine was evaluated after 1 hour treatment in differentiated Caco-2 cells (enterocytes) grown on Transwell® supports, before and after in vitro simulated intestinal digestion. Vinpocetine was applied at the apical side and its diffusion through the enterocytes barrier was detected by measuring the compound in the apical and basolateral compartments by LC-MS/MS analysis. Quantitative method was set up using tabersonine as internal standard. The separation was achieved using a reverse phase C-18 column, while detection by triple quadrupole (TQ) after ESI+ ionization.

The percentage of vinpocetine diffused through the enterocyte barrier was 8.1%. After digestion, only 3.8% of vinpocetine was recovered indicating that the molecule is unstable at intestinal conditions. Interestingly, only 0.003 ng/mL (0.017%) of the total amount of vinpocetine (17.52 ng/mL) recovered following intestinal digestion was absorbed.

The present study reports a suitable analytical method to quantify the intestinal absorption of vinpocetine; moreover, our results underline the importance of intestinal digestion in determining the poor bioavailability of vinpocetine.

[1] Patyar, S. Pharmacological Reports 2011, 63, 618 – 628.

[2] Szakacs, T. Pol. J. Pharmacol. 2001, 53, 623.