Title:Pharmacokinetics-Pharmacology Disconnection of Herbal Medicines and its Potential Solutions with Cellular Pharmacokinetic-Pharmacodynamic Strategy
VOLUME: 13 ISSUE: 5
Author(s):Jingwei Zhang, Fang Zhou, Meng Lu, Wei Ji, Fang Niu, Weibin Zha, Xiaolan Wu, Haiping Hao and Guangji Wang
Affiliation:Key Lab of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing, Jiangsu, 210009, P.R. China.
Keywords:Cellular pharmacokinetics-pharmacodynamics, pharmacokinetics-pharmacology disconnection, herbal medicines, subcellular distribution, drug transporter, metabolic enzyme, Pharmacology, behaviours, tanshinone IIA, anticancer agent, chemical constituents, toxicological evaluations, therapeutic
Abstract:Recently, there is a global trend of using herbal medicines to treat various chronic diseases and promote health. But the controversy
over the safety and efficacy of herbal medicines is a focus of attention, primarily because of the many unknown and unrevealed
natures of herbal medicines, which strongly restricts their application and development. Pharmacokinetics is a bridge linking the herbal
medicines and their pharmacological responses. It is assumed in traditional pharmacokinetics that an excellent drug should have appropriate
pharmacokinetic behaviours and its pharmacological effect is related with plasma drug concentrations. However, most herbal
medicines exhibit excellent pharmacological responses despite poor pharmacokinetic behaviours. As most drugs are intracellulartargeted,
we put forward cellular pharmacokinetic-pharmacodynamic strategy, which is focused on the intracellular fate of drugs. This
strategy could partially explain the marked pharmacological activities of herbal medicines from their intracellular pharmacokinetic behaviours,
rather than their plasma concentrations. It is a helpful complementarity to traditional pharmacokinetics, and takes a potential
role in the research and development of new herb-origined drugs. In this review, the pharmacokinetics-pharmacology disconnections of
herbal medicines (such as ginseng, berberine and danshen) are retrospected. Then our proposed cellular pharmacokineticpharmacodynamic
strategy, its characteristics, as well as its research procedures are described, followed by the subcellular distributions
of drug transporters and metabolic enzymes which are the determinants of cellular pharmacokinetics-pharmacodynamics. Finally, our
successful applications of cellular pharmacokinetic-pharmacodynamic strategy in elucidating ginsenoside Rh2 as an adjuvant agent and
tanshinone IIA as an anticancer agent are illustrated.
