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.
Key words
Voacanga africana
- Apocynaceae - voacangine - hERG channel -
in vivo
- population pharmacokinetics - Wistar rat plasma
