WS®1375 is the pharmaceutically active ingredient in Vitango®, a traditional herbal medicinal product used as adaptogen for the treatment of fatigue and other stress associated symptoms. The extract is prepared from the roots and rhizomes of Rhodiola rosea L. The aim of the investigation was to determine potential drug interaction effects of WS®1375. Of the 57 cytochrome P450 isoenzymes encoded by the human genome only 5 enzymes are responsible for the oxidative metabolism of 95% of all drugs (CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A4).1 We investigated the inhibitory/stimulatory effects of WS®1375 in microsomes, prepared from freshly isolated human hepatocytes. To get comprehensive information on the inhibitory effects the activity of all five major CYP isoenzymes was measured whereas the possible induction potential of WS®1375 was investigated only on the inducible isoenzymes CYP1A2 and CYP3A4. The IC50 values for inhibition were 1A2=63µg/ml, 2C9=77µg/ml, 2C19=75µg/ml, 2D6=25µg/ml and 3A4=104µg/ml. A more than 7-fold induction was observed for positive controls in the induction experiments confirming the functional state and the validity of the test system. The extract did not induce the catalytic activity of the cytochrome isoenzymes tested up to a concentration of 100µg/ml. Conclusion: The IC50 values for all CYP isoenzymes in the inhibition experiments were between 25µg/ml and 104µg/ml and thus far away from clinical relevant plasma concentrations. These data in combination with the lack of induction potential clearly demonstrates that WS®1375 is devoid of a clinical relevant interaction potential.
References: 1. Johnson, W.W. (2008) Drug Metabolism Reviews, 40:101–147.
