Translational Research Insights into Pharmacokinetic Herb-Drug Interactions

Haiping      Hao; Xiao      Zheng; Ping      Li; Guangji      Wang

doi:10.2174/138920011797470155

Abstract

Translational research is an emerging discipline that aims to fill the gap through the whole pipeline from bench to bedside. This review highlights the importance and urgency of incorporating translational research into the study of pharmacokinetic herb drug interactions (PHDI), based on an intensive discussion on the controversial and inconsistent reports from preclinical to clinical, in vitro to in vivo, and across different studies concerning PHDI. Current controversial and dispersed reports confer poor translational capacity of experimental research data to guiding the clinical practices. We propose that the herbal complexities in their chemical compositions, biphasic and tissue-specific effects of enzymes, and the present incomplete understanding of the disposition properties of herbal medicines themselves; and the enzymatic complexities in the species differences, individual genotype and phenotype, differential regulation during healthy and pathological conditions, substrate dependent modulations, and their interplay with transporters, collectively constitute the major translational blocks in PHDI from experimental research to daily clinical practice. In clinical considerations, this review indicates that PHDI are far from clear based on the isolated preclinical findings, and that the intestine is a much more susceptible site than liver when subjected to herbal regulations, and that enzymatic induction could be more predominant than inhibition upon chronic ingestion of herbal medicines. Hopefully, this review would be helpful for better understanding the nature of hurdles in PHDI research, and for igniting the future translational research initiatives.

Keywords: Herb drug interactions, pharmacokinetics, cytochrome P450, translational research, translational blocks, Pharmacokinetic Herb Drug Interactions (PHDI), Biotransformation, flavonoids, Drug Metabolizing Enzymes (DMEs), hepatocytes