[Research advance in multi-component pharmacokinetics of Chinese herbal extracts in recent five years].

The multi-component pharmacokinetic study of Chinese herbal extracts elaborates the in vivo processes,including absorption,distribution,metabolism,and excretion,of multiple bioactive components,which is of significance in revealing pharmacodynamic material basis of Chinese herbal medicine. In recent years,with the innovation in ideas,and development of techniques and methods on traditional Chinese medicine( TCM) research,the pharmacokinetic studies of Chinese herbal extracts were extensively performed,and notable progress has been made. This paper reviewed the advancement of multi-component pharmacokinetics of Chinese herbal extracts in recent five years from analysis technology of biological sample,the pharmacokinetic characteristics of Chinese herbal medicine with complex system,and the impacts of processing and pathological state on pharmacokinetics of Chinese herbal extracts,aiming to provide a reference for quality control,product development and rational medication of Chinese herbal extracts.

[Advance on pharmacokinetics study of traditional Chinese medicine injections in recent ten years].

Traditional Chinese medicine(TCM) injections boast a definite efficacy and have been widely used in clinic. However, the problems in medication safety have been attracted increasing attention. Pharmacokinetics is of significance to guiding TCM injection administration regimen design and improving safety and effectiveness in clinical use. In recent years, with the improvement of ideas, technology and methods of TCM studies, the pharmacokinetic studies of TCM injections have been broadly performed, with a notable progress. This paper reviewed the advance in pharmacokinetics studies of TCM injections in recent ten years, which mainly focused on pre-clinical concentration-time course, distribution, metabolism and excretion in vivo based on analysis techniques, pharmacokinetic interactions of constitutes, impact of pathological state, pharmacokinetic interactions between TCM injection and chemical drugs, and clinical pharmacokinetics studies of TCM injections, in the expectation of providing reference for studies on quality control, product development and rational clinical use of TCM injections.

[Application progress of proteomic in pharmacological study of Chinese medicinal formulae].

Chinese medicinal formulae are the important means of clinical treatment in traditional Chinese medicine. It is urgent to use modern advanced scientific and technological means to reveal the complicated mechanism of Chinese medicinal formulae because they have the function characteristics of multiple components, multiple targets and integrated regulation. The systematic and comprehensive research model of proteomic is in line with the function characteristics of Chinese medicinal formulae, and proteomic has been widely used in the study of pharmacological mechanism of Chinese medicinal formulae. The recent applications of proteomic in pharmacological study of Chinese medicinal formulae in anti-cardiovascular and cerebrovascular diseases, anti-liver disease, antidiabetic, anticancer, anti-rheumatoid arthritis and other diseases were reviewed in this paper, and then the future development direction of proteomic in pharmacological study of Chinese medicinal formulae was put forward. This review is to provide the ideas and method for proteomic research on function mechanism of Chinese medicinal formulae.

[Research progress of pharmacokinetics and pharmacodynamics of total glucosides of peony in hepatoprotective effects].

Total glucosides of peony (TGP), containing the effective components of paeoniflorin (Pae), albiflorin (Alb) and so on, are effective parts of Radix Paeoniae Alba. And it possesses extensive pharmacological actions, one of which is hepatoprotective effect. In recent years, abundant of pharmacokinetics and pharmacodynamics research of TGP in hepatoprotective effects have been performed. However, the relative medicine of TGP in hepatoprotective effect has not been developed for clinical application. In order to provide reference for the development and rational clinical application of TGP, the research progresses of pharmacokinetics and pharmacodynamics of TGP in hepatoprotective effect were summarized in this paper. Pharmacokinetics research has clarified the process of absorption, distribution, metabolism and excretion of TGP in vivo, and liver injury disease can significantly influence its metabolic processes. Pharmacodynamics studies suggested that TGP can protect against acute liver injury, non-alcoholic fatty liver diseases (NAFLD), chronic liver fibrosis and liver cancer. However, the action mechanism and in vivo process about hepatoprotective effects of TGP have not been clearly revealed. How liver injury influences the metabolism of TGP and its integrated regulation through multiple targets need to be further studied. The combined pharmacokinetics and pharmacodynamics studies should be performed in favour of medicine development and clinical application of TGP in hepatoprotective effects.

[Study on PK-PD characteristics of ginsenoside Rg1 and Rb1, in rats with myocardial ischemia following intravenous administration of shengmai injection].

It is the objective of this paper to study pharmacokinetics-pharmacodynamics (PK-PD) characteristics of ginsenoside Rg1 and Rb1 on the effect of inducing nitric oxide (NO) release after intravenous administration of Shengmai injection to rats with myocardial ischemia. The model of myocardial ischemia rats was produced by subcutaneous injection of isoproterenol. The serum samples were collected at different time points after intravenous administration of Shengmai injection to rats with the dose of 10.8 mL x kg(-1). The concentrations of ginsenoside Rg1 and Rb1 in serum were determined, and then the concentration-time curves were drawn. Pharmacokinetic parameters of ginsenoside Rg1 and Rb1 were calculated after the construction of pharmacokinetic models. Meanwhile, NO2- and NO3-, the metabolites of NO, in serum were determined, and then the effect-time curve was drawn. The combined PK-PD model was established based on the theory of effect compartment by Sheiner et al. Then pharmacodynamic parameters were calculated. The results indicated that the pharmacokinetics of ginsenoside Rg1 and Rb1 conformed to a two-compartment model. Ginsenoside Rg1 and Rb1 exhibited quick and slow elimination in rats respectively. The effect of Shengmai injection on inducing NO release did not relate directly with and lagged behind the concentrations of ginsenoside Rg1 and Rb1 in serum. The effect exhibited good correlation with ginsenoside Rg1 and Rb1 levels in effect compartment. The relationship between effect and serum concentration fits Sigmoid-E(max) model. This study successfully established the combined PK-PD model of ginsenoside Rg1 and Rb1 after intravenous administration of Shengmai injection to rats. The model can efficiently predict the concentration and effect of Shengmai injection in vivo.

Tissue distribution and excretion of herbal components after intravenous administration of a Chinese medicine (Shengmai injection) in rat.

Shengmai injection, consisting of Panax ginseng, Radix ophiopogonis and Schisandra chinensis, is a widely used Chinese medicine for the treatment of various cardiovascular diseases. In this study, tissue distribution and excretion of its multiple active components including protopanaxatriol-type (Ppt-type) ginsenosides (ginsenoside Rg1, Re, Rf and Rg2), protopanaxadiol-type (Ppd-type) ginsenosides (ginsenoside Rb1, Rd and Rc), ophiopogonin (ophiopogonin D), and lignan (schisandrin, schisandrol B and schizandrin B) in rat after single intravenous administration of Shengmai injection were reported. Ppt-type ginsenosides exhibited quick and wide distribution from blood into tissues and were eliminated rapidly through biliary, urinary and fecal excretions. Ppd-type ginsenosides Rb1, Rd and Rc distributed quickly from blood to all tissues but exhibited slow elimination by biliary and urinary excretions. Ophiopogonin D was excreted into bile with no urinary and fecal excretion, indicating its elimination in the form of secondary metabolites. Schisandrin, schisandrol B and schizandrin B was found to distribute quickly from blood into most tissues and had accumulation in these tissues. Very low biliary, urinary and fecal excretion implied that lignan was mainly excreted in the form of their metabolites. This study produced a first hand in vivo tissue distribution and dynamic profiles of the active components of Shengmai injection, providing valuable information for drug development and clinical application of Shengmai injection.

[Prediction of plasma protein binding of cephalosporins from polar molecular surface areas].

OBJECTIVE: To predict the plasma protein binding rate of cephalosporins from their molecular structural parameters. METHODS: The minimum energy conformations of cephalosporins were obtained from the optimization of the standard molecular geometry with the semiempirical self-consistent field molecular orbital calculation AM1 method; Mont Carlo method was used to calculate the polar molecular surface areas; the stepwise multiple regression analysis was used to obtain the correlation equations. RESULTS: The plasma protein binding rate of cephalosporins (fb) was well correlated with their molecular weights (MW) and surface areas of hydrogen-bonding donors (SH). The regression equation was: fb=0.5057+2.861x10(-3) MW-0.1572SH+4.714x10(-3) SH2(n=22, r=0.9042). CONCLUSION: Plasma protein binding of cephalosporins is closely related with their lipophilicity and hydrogen- bonding potential. The plasma protein binding rate of cephalosporins can be predicted from their molecular weights and surface areas of hydrogen-bonding donors.

[Prediction of human intestinal absorption from net polar atomic charges of drug molecules].

OBJECTIVE: To predict human intestinal absorption and permeability coefficients in Caco-2 cell monolayers from net polar atomic charges of drug molecules. METHODS: The net atomic charges and the volumes of drug molecules were obtained with the semiempirical self-consistent field molecular orbital calculation CNDO/2 method and Mont Carlo method respectively, using the minimum energy conformation obtained from the optimization of the standard molecular geometry with the molecular mechanics MM+ method. The stepwise multiple regression analysis was used to obtain the correlation equations. RESULT: Both percent of human intestinal absorption and permeability coefficients in Caco-2 cell monolayers of drug molecules were well correlated with the sum of the net atomic charges of all hydrogen-bonding donors (sigmaQH) and the sum of the net atomic charges of all hydrogen-bonding acceptors (sigmaQN, 0). The more the net positive atomic charges of hydrogen-bonding donors and the net negative atomic charges of hydrogen-bonding acceptors, the less were the percent human intestinal absorption and permeability coefficients in Caco-2 cell monolayers of drug molecules. CONCLUSION: Drug absorption in human intestines is closely related with its hydrogen-bonding potential. The drug molecules with weaker hydrogen-bonding potential have greater percent human intestinal absorption. The net polar atomic charges can be computed simply, so they can be used in high throughput screening of oral drugs.