源于中医临床的中药复方功效的现代研究思路与方法

中药复方是中医临床用药的主要方法与手段,中药复方功效是指在中医药理论指导下,对多味中药治疗作用的概括与总结。随着现代科学技术的发展,科学、有机地阐释复方功效的科学内涵,一直以来都是中医药基础研究的难点。本文就中药复方功效现代研究的思路与方法进行了深入探讨与总结,极大地丰富了中药复方功效现代研究的内容,促进了中药复方的研究和发展。

Population pharmacokinetics of paeoniflorin in guanxin Ⅱ prescription

To evaluate the effect of components in Guanxin Ⅱ prescription on the pharmacokinetic profiles of paeoniflorin. Plasma concentration of Paeoniflorin in rats after intravenous injection of Paronia Pall Extract （PPE） and oral administration of PPE and three types of decoctions in Guanxin Ⅱ prescription, respectively, were determined by HPLC analyses. NONMEM （nonlinear mixed-effect modeling） method was used to analyze full set of pharmacokinetic data directly. A two-compartment model with first-order degradation in absorption compartment was employed for the data analysis. The mean of population parameters, CL1, V1, CL2, V2, Ka0, and Kal, were measured to be 0.509 L/h, 0.104 L, 0.113 L/h, 0.123 L, 0.135/h, and 0.0135/h, respectively. Inter-individual variabilities were estimated and dose formulation （DF） was identified as a significant covariate of Ka 1, Ka0, and V1. It is concluded that the pharmacokinetic behaviors of paeoniflorin in rats can alter with different dose formulations.

Early metabolism evaluation making traditional Chinese medicine effective and safe therapeutics

Increasing attention is being paid to the scientific evaluation of traditional Chinese medicine （TCM）. As many TCMs are capable of biotransformation in the gastrointestinal tract, attention to biotransforrnation of TCM in the gastrointestinal tract may lead to discovery of the active components and active mechanisms. In this article, we review reports that host metabolic enzymes and intestinal bacteria may be responsible for the metabolism of TCM. Good understanding of the in vivo course of TCM will help us to know how to conduct metabolism evaluation of TCM by using in vitro human-derived system. This evaluation system will create new views on TCM as effective and safe therapeutic agents.

P-glycoprotein mediated interactions between Chinese materia medica and pharmaceutical drugs

P-glycoprotein(P-gp)is an important transmembrane ATP-binding cassette(ABC)drug efflux transporter expressed in various human tissues such as the intestines,liver,kidneys,and bloodbrain barrier.It limits the intracellular concentration of xenobiotics by pumping them out of the cells,affecting drug pharmacokinetics and therapeutic effects.With its broad substrate specificity,it has the potential to remove a wide range of drugs from Chinese materia medica(CMM),including conventional medicines and active compounds.Increasing evidence has confirmed the superior therapeutic effectiveness of CMM in treating a wide range of diseases worldwide,as well as in conjunction with western drugs.As a result,herbal medicine-drug compounds have prompted widespread concern,with the majority of these interactions involving transporters such as P-gp.This review systematically summarizes the inhibition or induction of P-gp expression/function by active CMM compounds and the underlying regulatory mechanisms.It will aid in improving understanding of the synergistic or inhibiting effects associated with transporter P-gp as well as rational safety concerns for using CMM,particularly in combination with drugs.

Effects of Rong Shuan capsule, Xue Zhi Kang capsule, Xin Yuan capsule and Songling Xue Mai Kang capsule on the pharmacokinetics of clopidogrel active metabolite in rats

In the present study, we aimed to examine the effects of Rong Shuan capsule, Xue Zhi Kang capsule, Xin Yuan capsule and Songling Xue Mai Kang capsule on the pharmacokinetics of clopidogrel active metabolite（CAM）. The traditional Chinese medicines（TCMs） Rong Shuan capsule, Xue Zhi Kang capsule, Xin Yuan capsule and Songling Xue Mai Kang capsule are widely used to treat cardiovascular disease in China. They are often prescribed in combination with clopidogrel, a common anti-platelet Western drug. We investigated the influence of the four TCMs on CAM pharmacokinetics following administration at human dose in rats. Pharmacokinetic parameters were determined following oral（PO） administration of clopidogrel（7.5 mg/kg） with or without Rong Shuan capsule（75 mg/kg, PO）, Xue Zhi Kang capsule（60 mg/kg, PO）, Xin Yuan capsule（120 mg/kg, PO）, or Songling Xue Mai Kang capsule（150 mg/kg, PO）. Compared with the animals in the control group, Xue Zhi Kang capsule significantly decreased the area under the plasma concentration-time curve（AUC_（0-t）） of the CAM derivative by 25.4%. However, the t1/2 and Vz/F of CAM derivative were significantly increased by 43.6% and 70.7%, respectively. It was also observed that the pharmacokinetic parameters were altered in groups pretreated with Rong shuan capsule, Xin yuan capsule or Songling Xue mai kang capsule compared with the control group, but not significant. This study indicated that Xue Zhi Kang capsule had an effect on the formation and metabolism of CAM. Therefore, in the beginning of co-administration of Xue Zhi Kang capsule and clopidogrel, the anti-platelet efficacy might be compromised because of the decreased formation of CAM. Otherwise, long-time co-administration might lead to side effects by the prolongation of the t1/2 and Vz/F increase of CAM.