In vitro and in vivo Inhibition of Cytochrome P450 Mediated Metabolism by Chinese Herbal Constituents

Abstract

Herbs have been used for a long time in several traditional practices, particularly in the Asian countries. However, documentation in the context of their safety evaluation is sometimes scarce and the people can consume them as home remedies or in combination with prescription medicines, which sometimes may be fatal. A sound knowledge of the mechanisms of herbal drug interactions is necessary for assessing and minimizing clinical risks, especially for drugs with a narrow therapeutic index are used. This made substantial concern regarding food or herbal drug interactions, and has also stimulated numerous research to fulfill the knowledge in this particular area. Such studies of the potential drug interactions caused by herbal extracts through CYP enzymes mediated drug metabolism may assist health practitioners and clinicians to evaluate the safety and effectiveness of herbal therapy. The aims of this thesis were to investigate the in vitro inhibition potential and inhibitory mechanisms of the three purified herbal constituents towards CYP enzymes metabolic activities in order to evaluate the interaction potentials of these herbal constituents with conventional drugs. Furthermore, on the basis of the in vitro results, tetrahydropalmatine was selected to be investigated its impact on the pharmacokinetics of probe drugs for CYP1A2, 2D6 and 3A4 isoenzymes in Beagle dogs using a cocktail method to evaluated possible clinical relevance of herb-drug interactions in clinical therapy.