Research advance in multi-component pharmacokinetics of Chinese herbal extracts in recent five years / 中国中药杂志

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 / 中国中药杂志

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.

Research progress of pharmacokinetics and pharmacodynamics of total glucosides of peony in hepatoprotective effects / 中国中药杂志

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.

Application progress of proteomic in pharmacological study of Chinese medicinal formulae / 中国中药杂志

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.

Rapid determination of 15 chemical drugs illegally added into slimming Chinese patent medicines and health foods by UPLC-MS/MS / 中草药

Objective: To establish a rapid and accurate method for the determination of 15 chemical drugs which were illegally added into the slimming Chinese patent medicines (CPM) and health foods. Methods: The UPLC-MS/MS method was adopted. The samples were extracted with methanol by ultrasonic processing and separated on a Waters Acquity BEH C18 column (100 mm × 2.1 mm, 1.7 μm) with 0.1% formic acid methanol (A) -0.1% formic acid water (B) as mobile phase by gradient elution (0-3 min, 33%-45% A; 3-5 min, 45%-55% A; 5-7 min, 55%-70% A; 7-9 min, 70%-80% A; 9-10 min, 80%-90% A; 10-11 min, 90%-33% A; 11-13 min, 33% A at a flow rate of 0.2 mL/min, and the column temperature was 40℃. A positive-ion (ESI+) source and an MRM mode were used to separate and quantitatively determine 15 chemical drugs. The obtained molecular ions, fragment ions, and retention time for MRM channels were used to identify the 15 kinds of drugs by comparison with those of reference substances. The obtained peak areas were used to determine the accurate contents of chemical drugs in CPM and the health foods. Results: A good resolution of 15 kinds of chemical drugs, including terbutaline hydrochloride, ephedrine hydrochloride, theophylline, caffeine, doxofylline, clenbuterol hydrochloride, tulobuterol hydrochloride, bambuterol hydrochloride, fenfluramine hydrochloride, furosemide, indapamide, phenolphthalein, sibutramine hydrochloride, N-demethylated sibutramine hydrochloride, and hydrochloric acid N,N-dinor sibutraminel, was obtained under this UPLC and MS/MS condition. The limits of qualitation and quantitation were in the range of 0.1-5.0 ng/g and 0.3-15.0 ng/g. The standard addition recoveries were in the range of 91.8%-110.8%. In the 86 batches of samples (including capsules, granules, and other different matrix types) were detected in the 74 batches of added chemicals, the positive rate was 86.0%. Sibutramine hydrochloride (39 batches), furosemide (20 batches), phenolphthalein (23 batches), theophylline (1 batch), and caffeine (15 batches) were checked out in the samples, 22 batches of which two kinds were checked out, one batch of which three kinds were checked out. By contrast, the products which were not clearly marked manufacturer illegally added more seriously. Conclusion: The method is simple, accurate, and highly sensitive, which can be used for the determination of illegally added chemical drugs in slimming CPM and health foods.

Study on PK-PD characteristics of ginsenoside Rg1 and Rb1, in rats with myocardial ischemia following intravenous administration of shengmai injection / 中国中药杂志

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.

A simple and accurate method to determine nitrite and nitrate in serum based on high-performance liquid chromatography with fluorescence detection.

A simple method for accurate determination of nitrite and nitrate in serum was proposed to avoid the variation of nitrate reduction. For nitrite determination, serum samples were directly precipitated with methanol pre-nitrate conversion, and then the supernatant reacted with 2,3-diaminonaphthalene (DAN) to form 2,3-naphthotriazole (NAT), which was quantitatively analyzed by high-performance liquid chromatography coupled with fluorescence detection (HPLC-FL). For nitrate determination, samples were firstly heated at 70°C for 10 min to inactivate endogenous reductase-inhibiting proteins, then nitrate in the samples was quantitatively reduced to nitrite by reductase added experimentally. The difference in total nitrite concentrations between pre- and post-nitrate conversion was used to calculate the amount of nitrate in the samples. In addition to good specificity, high sensitivity, satisfactory accuracy and reproducibility, our method is simple and suitable for the quantitative determination of nanomolar level of nitrite and nitrate in a large number of serum samples.

Prediction of plasma protein binding of cephalosporins from polar molecular surface areas / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To predict the plasma protein binding rate of cephalosporins from their molecular structural parameters.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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).</p><p><b>CONCLUSION</b>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.</p>

Prediction of human intestinal absorption from net polar atomic charges of drug molecules / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To predict human intestinal absorption and permeability coefficients in Caco-2 cell monolayers from net polar atomic charges of drug molecules.</p><p><b>METHODS</b>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.</p><p><b>RESULT</b>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.</p><p><b>CONCLUSION</b>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.</p>