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Front. Pharmacol. | doi: 10.3389/fphar.2019.01243

Pharmacokinetic interaction of green rooibos extract with atorvastatin and metformin in rats

  • 1South African Medical Research Council, South Africa
  • 2Department of Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University, South Africa
  • 3Division of Medical Physiology, Faculty of Medicine and Health Sciences, Stellenbosch University, South Africa
  • 4Department of Biochemistry and Microbiology, Faculty of Science and Agriculture, University of Zululand, South Africa
  • 5Institute for Deciduous Fruit, Vines and Wine, Agricultural Research Council, South Africa
  • 6Department of Food Science​, Faculty of AgriSciences, Stellenbosch University, South Africa
  • 7Mass Spectrometry Unit, Central Analytical Facility, Stellenbosch University, South Africa

An aspalathin-rich green rooibos extract (Afriplex GRT™) has demonstrated anti-diabetic and hypolipidemic properties, while also moderately inhibiting CYP3A4 activity, suggesting a potential for herb-drug interaction. The present study, therefore, evaluated the effects of orally administered GRT on the pharmacokinetics of atorvastatin and metformin in Wistar rats. Wistar rats were orally treated with GRT (50 mg/kg BW), atorvastatin (40 mg/kg BW) or metformin (150 mg/kg BW) alone or 50 mg/kg BW GRT in combination with 40 mg/kg BW atorvastatin or 150 mg/kg BW metformin. Blood samples were collected at 0, 10, 30 min, and 1, 2, 4, 6 and 8 h and plasma samples obtained for LC-MS/MS analyses. Non-compartment and two-compartment pharmacokinetic parameters of atorvastatin and metformin in the presence or absence of GRT were determined by PKSolver version 2.0 software. Membrane transporter proteins, ATP-binding cassette sub-family C member 2 (Abcc2), solute carrier organic anion transporter family, member 1b2 (Slco1b2), ATP-binding cassette, sub-family B (MDR/TAP), member 1A (Abcb1a) and organic cation transporter 1 (Oct1) mRNA expression was determined using real-time PCR expression data normalized to β-actin and hypoxanthine (guanine) phosphoribosyl transferase (HPRT), respectively. Co-administration of GRT with atorvastatin substantially increased the maximum plasma concentration (Cmax) and area of the plasma concentration-time curve (AUC0-8) of atorvastatin by 5.8-fold (p = 0.03) and 5.9-fold (p = 0.02), respectively. GRT had no effect on the plasma levels of metformin. GRT increased Abcc2 expression, whilst the combination of GRT and atorvastatin did not significantly alter the expression of Sclo1b2 or Oct1. Co-administration of GRT with atorvastatin in rats may lead to higher plasma concentrations and therefore to an increase of the exposure to atorvastatin.

Keywords: Rooibos (Aspalathus linearis), atorvastatin, transporters, Wistar, Rats

Received: 15 Mar 2019; Accepted: 27 Sep 2019.

Copyright: © 2019 Patel, Muller, Joubert, Rosenkranz, Taylor, Louw and Awortwe. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Christo Muller, South African Medical Research Council, Cape Town, South Africa,