title: Pharmacokinetics-pharmacology disconnection of herbal medicines and its potential solutions with cellular pharmacokinetic-pharmacodynamic strategy.
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.
authors.affiliation: Key Lab of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, Jiangsu, China.
authors.forename: Jingwei
authors.initials: J
authors.lastname: Zhang
authors.forename: Fang
authors.initials: F
authors.lastname: Zhou
authors.forename: Meng
authors.initials: M
authors.lastname: Lu
authors.forename: Wei
authors.initials: W
authors.lastname: Ji
authors.forename: Fang
authors.initials: F
authors.lastname: Niu
authors.forename: Weibin
authors.initials: W
authors.lastname: Zha
authors.forename: Xiaolan
authors.initials: X
authors.lastname: Wu
authors.forename: Haiping
authors.initials: H
authors.lastname: Hao
authors.forename: Guangji
authors.initials: G
authors.lastname: Wang
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D002468:Cell Physiological Phenomena; D006801:Humans; D028321:Plant Preparations / Q000493:pharmacokinetics* / Q000494:pharmacology*; D010946:Plants, Medicinal / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D028321:Plant Preparations