Pharmacokinetic herb–drug interactions with traditional Chinese medicine: progress, causes of conflicting results and suggestions for future research

Abstract

Traditional Chinese medicine (TCM) has a long history of medical use in China and is still used worldwide. Unexpected herb-drug interactions (HDIs) may lead to adverse drug reactions or loss of therapeutic efficacy of the victim drug. Here, based on searches of Medline, EBSCO, Science Direct and Web of Science using various keywords, we summarize the TCM-derived pharmacokinetic HDIs that were reported from 1990 to 2015 and discuss the underlying mechanisms. In general, many pre-clinical and clinical pharmacokinetic HDIs have been reported. Our searches show that TCMs cause pharmacokinetic interactions with therapeutic drugs mainly by inhibiting or inducing drug-metabolizing enzymes and transporters. However, most of the interactions result from a small number of prescription medications and the actual potential for harm is low. Moreover, such HDIs can be avoided by discontinuing the TCMs. Despite the extensive number of reports on TCM-derived HDIs, the findings are frequently conflicting and can be confusing. The causes of the conflicts vary, but we classified them into three basic categories as follows: (1) complicated nature and poor quality control of TCMs, (2) different responses of various test systems to TCM exposure and (3) diverse study designs. Accordingly, we propose rational study designs for future HDI research. We also propose that a specific authoritative guide be established that provides recommendations for HDI studies. This review provides insights into the progress and challenges in TCM-derived pharmacokinetic HDI research.

Inhibitory Effects of Aschantin on Cytochrome P450 and Uridine 5′-diphospho-glucuronosyltransferase Enzyme Activities in Human Liver Microsomes

“…Herbal medicines and their constituents may interact with cytochrome P450 (CYP) and uridine 5′-diphospho-glucuronosyltransferases (UGTs), increasing the possibility of herb-drug interactions [8][9][10][11][12][13]. Several medicinal herbs, including Allium sativum, Camellia sinensis, Ginkgo biloba, Glycyrrhiza glabra, Coptidis rhizoma,Silybi fructus, and St. John's wort are associated with herb-drug interactions attributable to inhibition and/or induction of drug-metabolizing enzymes [14][15][16][17].…”

“…It exhibits various biological activities including peroxynitrite scavenging capacity, inhibition of inducible NO synthetase, antiplasmodial activity, Ca 2+ -antagonistic activity, platelet activating factor-antagonistic activity, and chemo-preventative or therapeutic activity mediated via inhibition of mTOR kinase [2][3][4][5][6][7]. Herbal medicines and their constituents may interact with cytochrome P450 (CYP) and uridine 5′-diphospho-glucuronosyltransferases (UGTs), increasing the possibility of herb-drug interactions [8][9][10][11][12][13]. Several medicinal herbs, including Allium sativum, Camellia sinensis, Ginkgo biloba, Glycyrrhiza glabra, Coptidis rhizoma,Silybi fructus, and St. John's wort are associated with herb-drug interactions attributable to inhibition and/or induction of drug-metabolizing enzymes [14][15][16][17].…”

Integrating traditional Chinese medicines into professional community pharmacy practice in China – Key stakeholder perspectives

“…Furthermore, HMs and conventional medicines are often prescribed together for the treatment of disease or used informally as part of a self-care practice [17]. Pharmacokinetic interactions that result in the inhibition or induction of drug-metabolizing enzymes and transporters raise safety concerns and may impact treatment outcomes [18][19][20]. In addition to potential interactions, the component complexity of HMs and uncertainties regarding their safety and efficacy raises a need for healthcare professionals to be involved in stewarding the judicious use of HMs.…”

Inhibitory Effects of Dimethyllirioresinol, Epimagnolin A, Eudesmin, Fargesin, and Magnolin on Cytochrome P450 Enzyme Activities in Human Liver Microsomes

“…Herbal drugs (e.g., Hypericum perforatum , Ginkgo biloba , Camellia sinensis , Glycyrrhiza glabra , Allium sativum , Rhizoma Coptidis, and Fructus Silybi) and their constituents cause herb–drug interactions via the induction or inhibition of major drug-metabolizing enzymes, cytochrome P450 (CYP) and result in the toxicity and therapeutic failure of various concomitant drugs [21,22,23,24,25,26,27,28,29,30,31]. For the prediction of herb-drug interaction, it is necessary to investigate the in vitro inhibitory effects of herb drugs and the constituents on major human CYP enzyme activities.…”