Planta Med 2016; 82(11/12): 1030-1038
DOI: 10.1055/s-0042-107800
Pharmacokinetic Investigations
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Pharmacokinetics of hERG Channel Blocking Voacangine in Wistar Rats Applying a Validated LC-ESI-MS/MS Method[*]

Christina E. Mair**
1  Department of Pharmacognosy, University of Vienna, Vienna, Austria
,
Carolina de Miranda Silva**
2  Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil
,
Ulrike Grienke
1  Department of Pharmacognosy, University of Vienna, Vienna, Austria
,
Jadel M. Kratz
1  Department of Pharmacognosy, University of Vienna, Vienna, Austria
3  Departamento de Ciências Farmacêuticas, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil
,
Fernando Carreño
2  Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil
,
Estevan Sonego Zimmermann
2  Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil
,
Bibiana Verlindo de Araújo
2  Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil
,
Teresa Dalla Costa
2  Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil
,
Judith M. Rollinger
1  Department of Pharmacognosy, University of Vienna, Vienna, Austria
› Author Affiliations
Further Information

Publication History

received 07 March 2016
revised 15 April 2016

accepted 17 April 2016

Publication Date:
03 June 2016 (eFirst)

Abstract

Herbal preparations from Voacanga africana are used in West and Central African folk medicine and are also becoming increasingly popular as a legal high in Europe. Recently, the main alkaloid voacangine was found to be a potent human ether-à-go-go-related gene channel blocker in vitro. Blockage of this channel might imply possible cardiotoxicity. Therefore, the aim of this study was to characterise voacangine in vivo to assess its pharmacokinetics and to estimate if further studies to investigate its cardiotoxic risk are required. Male Wistar rats received different doses of voacangine as a pure compound and as a hydro-ethanolic extract of V. africana root bark with a quantified amount of 9.71 % voacangine. For the obtained data, a simultaneous population pharmacokinetics model was successfully developed, comprising a two-compartment model for i. v. dosing and a one-compartmental model with two first-order absorption rates for oral dosing. The absolute bioavailability of voacangine was determined to be 11–13 %. Model analysis showed significant differences in the first absorption rate constant for voacangine administered as a pure compound and voacangine from the extract of V. africana. Taking into account the obtained low bioavailability of voacangine, its cardiotoxic risk might be neglectable in healthy consumers, but may have a serious impact in light of drug/drug interactions and impaired health conditions.

* Dedicated to Professor Dr. Dr. h. c. mult. Kurt Hostettmann.


** These authors contributed equally to this work.


Supporting Information