A reversed-phase high performance liquid chromatography (HPLC) method for the rapid determination of ketoconazole in human plasma is described.The column was 15 cm?4.0 mm ID stainless steel packed with HITACHI GEL 3056 (ODS). A guard column (PRECOLUMN) 5 cm?5.0 mm packed with YWG-C18H37(40?m) was attached to the primary column.The mobile phase consisted of methanol:0.02 mol/L phosphate buffer (pH 7.61)(72:28, vol/vol) and the flow rate was 0.7 ml/ min.Chromatography was performed wih variable UV monitor at 217 nm.N-(p-bromo-phenyl)-2-amino-4. 5-dihydrothiazole was used as an internal standard.The retention time for hetoconazole and internal standard were 11 min 18 s and 7 mm 13 s, respectively. The detection limit was 10 ng.The average recoveries (2?g/ml) of within-day and between-day were 96.80?3 . 13% (CV- 3.23% ) and 92.68 ?2.09% (CV = 2.26), respectively.The pharmacokinetics of ketoconazole was studied by the above HPLC method after a single oral dose of 400 mg in six healthy subjects .The drug concentration-time curve was a two compartment open model with an equation C = 23 .3574e-0.2055t + 9. 5528e-0.1131t - 32.9102e-0.4229tThe pharmacokinetic parameters of ketoconazole obtained were as follows(mean value) : T1/2?=6.2060h, Cmax= 7. 6553?g/ml,Vd= 0.8375 L/Kg,CL = 0.0932 L/h/Kg.The results show that the HPLC method is rapid, sensitive, highly specific and accurate, and is suitable for the studies of pharmacokinetics and clinical monitoring of ketoconazole concentrations in human plasma.

A RP-HPLC method was described for the determination of plasma propafenone. The column was 25 cm?4. 0 mm ID stainless steel packed with ODS (5 ?m). The mobile phase consisted of CH3OH: HAC-NaAC: H2O (70: 15: 15, v/v), containing 0. 0584 mol/L diethylamine as a modifier. The flow rate was 1. 0 ml/min. Tetracaine was used as a internal standard. Chromatography was performed at 250 run with variable wavelength ultraviolet detector. The propafenone was first extracted from alkalized plasma with 2.0 ml of 2% (v/v) isoamyl alcohol in n-heptane, and then reextracted with 0. 3 mol/L H3PO4, 100?l. Linear calibration curve for propafenone was measured over the range of 50-1600 ng/ml, and correlation coefficient was 0. 9993. The recovery rate of the method was 88.82?6.39% (n =5), and the coefficient of variation was less than 10% (n = 10). The lowest determined level was 40 ng/ml.The pharmacokinetic parameters were measured by this method in 5 healthy volunteers after a single oral dose propafenone 300 mg. The mean pharmacokinetic parameters were as follows: t1/2 (Ka=0. 40?0. 15 h, t1/2 (K) =2. 81?0. 52 h, Tmax= 1. 88?0. 47 h, Cmax= 631. 67?453. 13 ng/ml, and AUC= 3843.06?3032. 80ng?h-1?ml-1..

The double drug interaction between propafenone (PF) and digoxin (D) was investigated in twelve healthy volunteers. The subjects were randomly divided into two subgroups and each group received PF, D, PF plus D at different administration plan, respectively. The serum D concentration (SDC) and plasma PF concentration (PPFC) were measured by fluorescence polarization immunoas-say (FPIA) and high performance liquid chromatography (HPLC), respectively. The concentration -time data of PF were inputted into an IBM/PC/XT microcomputer. The MCPKP - automatic pharmacokinetic program (worked out by Xia WJ) was employed for selection of the optimal compartment model and calculation of the pharmacokinetic parameters using weighted nonlinear least square regression.The results of this study showed that SDC (mean?SD) rose from 0.64?0.14 ng/ml to 0.83?0.17 ng/ml (mean increase 31.57?20.81%, P0.05), but there was great interindivi-dual variability. Although no normal man had serious adverse effects from the PF plus D interaction, in patients receiving D and PF simultaneously, the SDC should be monitored and the dosage of D readjusted if there is evidence of toxicity.

OBJECTIVE:To discuss how clinical pharmacists adapt the policy of New Medical Reform and to make sure the position and role of clinical pharmacists in order to increase the number of clinical pharmacists and to promote the development of clinical pharmacy.METHODS:The development of clinical pharmacy was compared between American and China.The status quo of the development of clinical pharmacy in China was analyzed.The influence of pharmaceutical administration of New Medical Reform on the development of clinical pharmacy was investigated.The development prospect of clinical pharmacists was proposed.RESULTS&CONCLUSION:The development of clinical pharmacy in China has a big gap compared with that of foreign countries.The factors such as the lag of education,the shortage of clinical pharmacists' quality,the unsound of policy protection,and the immature reform of health care system,all hinder the development of clinical pharmacy.Some relevant provisions of new health care system show that the government make up it's mind to promote rational use of drugs.Safe,economical and effective drug use is our target in the future.Government may draw up policy about professional certification of clinical pharmacists and labor assessment at first,which provide good future prospects and payment to attract more talent.

Research and development of new drugs refers to the whole process ranging from experimental study to marketing and clinical application. The research and development of new drugs in industrial countries focuses on drugs for infection, the cardiovascular system, the blood system, the central nervous system and tumors, and on adjuvant drugs, Biotech drugs, endocrinologic and metabolic drugs. At present most domestic new drugs are imported or from joint venture pharmaceutical companies, and most domestic pharmaceutical manufacturers are mainly involved in the production of old drugs. In addition, most domestic new drugs are patent drugs. The disadvantages of the Chinese pharmaceutical industry include small-scale production and low technology content. The main problems in new drug research and development include shortage of finance , poor conditions of industrialization and low ability of innovation. It is necessary and urgent to do our best to enhance the Chinese pharmaceutical industry with respect to technological exploitation and power of market control in the context of international competition through strategic merging and scale management.

OBJECTIVE: To study the time window of apoptosis and related genes expression of the myocardiocytes in sinoaortic-denervated(SAD) rats.METHODS SAD of shamoperation(Sham) was performed in male SD rats at the age of 10 weeks.After 4, 8, 16, 32 weeks, apoptotic cells were stained in situ using terminal dexynucleotidyl - transferase mediated -dUTP nick end labeling(TUNEL) .All stained results were analysed by computer image analysis techniques.Bel-2, Bax, Fas and Fas-L were detected using immunohistochemical method.RESULTS: Compared with Sham controls, the number of apoptotic myocardiocytes was significantly increased;The expressions of Bel - 2 were significantly decreased, whereas Bax,Fas and Fas-L were significantly increased in SAD rats.The ratio of Bcl-2/ Bax was decreased.CONCLUSION Apoptosis and dysregulation of related gene expressions may be involved in the myocardial remodeling in SAD rats.

OBJECTIVE:To establish a HPLC procedure to determine diclofenac sodium in human plasma.METHODS:The plasma sample was deproteinized by adding acetonitrile,A Hypersil-BDS(250?4.6mm,5?m)column with a mobile phase consisting of methanol-water-10%phosphate acid(60∶40∶1)was used,the detecting wavelength was276nm,column tem?perature was35℃.RESULTS:The linear range was20.50～2050.0ng/ml(r=0.9998,n=5),the detective limit was10ng/ml.The recovery was99.47%～105.4%with the within-day RSD from3.77%to5.81%(n=5),and the between-day RSD from4.93to8.96%(n=5)at three different concentrations.CONCLUSION:The method is simple,rapid and suitable for the pharmacokinetic study of diclofenac sodium.

Cytochrome P450 is an important kind of enzymes for the metabolism of drug and other endo-or xeno-biotics. Classification of metabolic enzymes, molecular biological characteristic of CYP3A4, CYP2D6, CYP2C9, CYP2C19, CYP2E1, CYP1A2 and CYP2A6 were described in this review. Influence of traditional Chinese medicine(TCM) on metabolic enzyme and its application in clinical drug therapeutics and drug development were also reviewed in this article.

Objective:To compare the pharmacokinetics and relative bioavailability of rapid oral disintegrating tablet of dimenhydrinate(RODTD) and those of market available tablet of dimenhydrinate(DMH).Methods: Eight healthy volunteers were evenly randomized into 2 groups,one group received RODTD(25 mg) and the other received available market tablet of dimenhydrinate(25 mg).The blood levels of DMH were determined by high performance liquid chromatography(HPLC) before and after drug administration in 2 groups.Chromatography conditions were: Nova-Pak C_(18)as chromatographic column, methanol triethylamine buffer((11),)flow rate: 1.0 ml/min,detection wavelength: 225 nm,and room temperature.The pharmacokinetics and relative bioavailability of RODTD and market available tablets were investigated.Results: The standard curve of DMH in the blank plasma was linear within the range of 5-500 ng/ml,with the regression equation being C=0.004 4 A+4.745 and R~(2)=(0.996.)The limit of detection was 2 ng/ml;the average recovery rate was(90.55?4.69)% and the RSD was 0.041%.The intra-day derivations of 3 different concentrations(low,middle,and high) of plasma were 9.27%,4.93%,and 2.95%,respectively((n=5),) and the inter-day derivations were 9.97%,3.81%,and 3.06%,respectively(n=5).Blood samples(3 ml) were subjected to HPLC assay and significant difference was found between the 2 forms of DMH. The pharmacokinetic parameters of RODTD were: AUC=(602.04?113.82) ng?h?ml~(-1),C_(max)=(95.86?21.28) ng?ml~(-1),and T_(Peak)=(1.8?0.32) h;the pharmacokinetic parameters of market available tablets were:AUC=(342.73?84.96) ng?h?ml~(-1),C_(max)=((46.34?)(10.32)) ng?ml~(-1),and T_(Peak)=(2.65?0.24) h.Statistical analysis showed there was significant difference in the relative bioavailability of 2 forms of DMH(P

Pharmacogenomics is defined as the study of the association between genetics and drug response. This review includes basic concepts of pharmacogenomics, heterogeneity of hypertension and antihypertensive drug responses, genes associate with drug metabolism, and individualized drug therapy. The knowledge of genes that influence the pharmacodynamic determinants of blood pressure response to antihypertensive medications has the potential to provide new insights not only into molecular mechanisms influencing drug response, but also into the role that these genes may play in determining interindividual differences in blood pressure level and the occurrence of hypertension.