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

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.