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Welcome to Chinese Journal of Clinical Pharmacology and Therapeutics,Today is Chinese

Table of Content

    Volume 7 Issue 1
    26 February 2002
    Apoptosis of osteosarcoma cell line pl-1 indnced by docitaxol in vitro
    PENG Lei, WANG Zhen, WANG Qing-Liang, CAO Yun-Xin, ZHU De-Sheng, ZHANG Zhi-Pei, WU Yin-Song, SHI Xin-You
    2002, 7(1):  1-4. 
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    AIM: To study the growth-inhibition and apoptosis-inducted by docitaxol in osteosarcomatous cells. METHODS: Docitaxol-induced osteosarcomatous cells were detected and observed with cell counting, morpho-logic observation, flow cytometry (FCM), and electron-microscope etc. RESULTS: Docitaxol could inhibit the growth of osteosarcomatous cells effectively at the concen-tration of 4 mg·L-1 in a time-dependent manner and fur-ther dose-dependent manner in a certain range. Osteosar-comatous cells were blocked during G1/M phage and in-duced to apoptosis.Cells undergoing apoptosis exhibited the following typical features;an apparent apoptoic peak during dection of cell cycle with FCM, chromatin' s cling to periphery of the shrunken nuclear, apoptitic body, and floccule condensed matrix with electron-microscope. Fur-ther, cells recultureed after being treated with docitaxol shortly were more apt to undergo apoptosis than cells treated with docitaxol continually. CONCLUSION: Be-cause of the ability to induce apopotisis, docitaxl shows a great potential in the treatment of osteosarcoma.
    Combined inhibitory effects of propofol and midazolam on macroscopic sodium currents in rat sympathetic ganglion neurons
    ZHENG Ji-Jian, ZHUANG Xin-Liang, DU Dong-Ping, MAO Qing-Hong, XU Guo-Hui
    2002, 7(1):  5-8. 
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    AIM: To study the interactions of propo-fol and midazolam on the whole-cell sodium channel cur-rents in rat sympathetic ganglion neurons.METHODS: Whole-cell patch-clamp recordings were made from enzy-matically isolated rat (7-10 d)superior cervical sympa-thetic ganglion neurons.Isobolographic analysis was ap-plied to evaluate the potency of combinations of propofol and midazolam on Na+channel currents.RESULTS: Under Vh = 80 mV and Vt =0 mV. Propofol and mida-zolam dose-dependently blocked Na+ currents with a mean drug concentration required to produce 50%current inhibition(IC50 ):33.12 μmol·L-1 and18.35 μmol·L-1; clinically relevant concentrations of propofol and midazo-lam reduced Na+ peak currents by 27.66%(P <0.01) and 19.88%(P <0.05).The IC50 values of midazolam combined with 1/4 and 3/4 IC50 propofol located in the 95% confidence limits of theoretical additive line; the IC50 values of midazolam combined with 1/2 IC50 propofol located under the 95%confidence limitsof theoretical ad-ditive line. CONCLUSION: Clinically relevant concen-trations of propofol and midazolam have direct and dose-dependent inhibition on the Na+ channel currents of rat sympathetic ganglion neurons.The interactions between propofol and midazolam at Na+ channel current are addi-tive, in addition to the synergism which equi-effective doses are used.Reduction of cardiovascular depression during co-inductionof propofol and midazolam may be rel-evant to the reduction of doses.
    Inhibitive proliferation and promotive apoptosis effects of oxysterols on vascular smooth muscle cells (VSMC)
    HONG Hua-Shan, LIN Lan, WANG Yi-Bo, ZHENG Guan-Yi, CHEN Liang-Long, CHEN Jian-Hua
    2002, 7(1):  9-13. 
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    AIM: To study the effects of cholestan-3β, 5α, 6β-triol (Triol ) and 25-hydroxycholesterol (25OH) on proliferation, apoptosis of vascular smooth muscle cells(VSMC) and to explore the effects and signifi-cance of oxysterols in atherogenesis.METHODS: VSMC of aorta of New Zealand white rabbit were cultured and i-dentified.VSMC incubated with or without Triol and 25OH or cholesterol, at different concentrations, was as experimental groups or control group.Cell proliferation was measured with WST-1.Cell apoptosis was evaluated by light and electron transmissionmicroscopy and terminal deoxynuocleotidyl transferase (TdT)-mediated dUPT nick-end labeling (TUNEL). RESULTS: The metabolic ac-tivity of VSMC wasnot different between at low dose (1× 10-9 -1 ×10-7 mol·L-1 ) of Triol and 25OH experi-mental groups and control group (P >0.05), but it de-creased significantly at higher dose (≥ 1 × 10-6 mol·L-1 ) of oxysterols groups (P <0.01). After being treated with higher dose(≥20×10-6 mol·L-1 ) of oxyterols, VSMC showed apoptosis of ultrastracture change including shrinkage, condensation of nuclear chro-matin, fragmentation nuclei and formation of apoptotic body.TUNEL revealed that Triol-induced apoptosis in VSMC was in a concentration-dependent manner.CONCLUSIONS: Triol and 25OH, at low dose, have not growth effect on VSMC, but at higher dose can induce VSMC apoptosis.Oxysterol-induced VSMC apoptosis may trigger plaque rupture and play an important role in atherogenesis.
    Effects of 9-(4-Ethoxycarboxylyphenoxy)-6,7-dimethoxy-1,2,3,4-te-trahydro acridine on learning and memory ability in mice
    SHENG Rui, LIU Guo-Qing
    2002, 7(1):  14-17. 
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    AIM: To study the effects of 9-(4-Ethoxycarboxylyphenoxy)-6,7-dimethoxy-1,2,3 4-te-trahydro acridine (EDT) on learning and memory abili-ties.METHODS: The step-down test and Y-maze test were adopted in this study. RESULTS: EDT (2.5,5,10 mg·kg-1, ig ×5 d) dose-dependently improved the impairment of memory acquisition, memory consolidation and memory retrieval induced by scopolamine, NaNO 2 and alcohol in mice. CONCLUSION: EDT can improve learning and mermory ability in mice.
    Effect of metronidazole on percutaneous absorption of l-menthol through changing the skin character in rabbits
    XU Wei-Ming, WANG Hui, FENG Xiao-Long
    2002, 7(1):  18-20. 
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    AIM: To investigate the effect of l-men-thol on percutaneous absorption of metronidazole through changing the skin character in rabbits.METHODS: Us-ing rabbit skin with different character as transdermal bar-rier, and l-menthol as transdermal enhancer, the ab-sorbance of metronidazole was determined with a two-cells diffusion apparatus in vitro, and its permeability was fig-ured out. RESULTS: The transdermal action of l-men-thol on percutaneous absorption of metronidazole was very evident when the corneum was eliminated;l-menthol and azone could increase the desposit function of metronida-zole in the intact skin, but had no effect on the skinwith-out corneum. The result also showed that the percuta-neous absorption and intact skins desposit function of metronidazole had no difference between l-menthol and a-zone. CONCLUSION: L-menthol can increase the per-cutaneous absorption of metronidazole. The site of the ac-tion is mainly the corneum which has desposit function.
    Effect of clarithromycin on pharmacokinetics of aminophylline at steady state in rabbits
    SUN Cheng-Chun, ZHAO Xiao-Yuan, CAO Yang, WANG Jing-Xiang
    2002, 7(1):  21-23. 
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    AIM: To investigate the effect of oral clarithromycin on serum concentrations of aminophylline at steady state and its pharmacokinetics in New Zealand rab-bits.METHODS: The serum concentration of amino-phylline was determined by FPIA in rabbits given(po) aminophylline or aminophylline combined with clar-ithomycin.The experiment was divided into 2 stages: (Ⅰ) the subjects only received a four-day course of oral aminophylline until steady state;(Ⅱ) aminophylline and clarithromycin were coadministrated from the d 5 to d 10. The dose of aminophylline was 30 mg·kg-1 and the dose of clarithromycin was 50 mg·kg-1 for each rabbit. The two series of pharmacokineticis parameters were tested by statistic analysis.RESAULTS: There was no significant variation in pharmacokinetic parameters between two stages.CONCLUSION: It is not necessary to change the therapeutic dose of aminophylline when the drug is taken in combination with clarithromycin.
    Protective effects of amitriptyline on glutamate-induced neurotoxicity in cerebral neuronal cultures
    XU Qing-Rong
    2002, 7(1):  24-26. 
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    AIM: To study the protective effects of amitriptyline (Ami) on glutamate-induced neurotoxicity in cultured rat cerebral cortical neurons.METHODS: Cor-tical neurons of fetal rat were cultured in vitro. The pro-tective effects of Ami on glutamate-induced neurotoxicity were observed.RESULTS: Exposure of rat fetus cerebral cells to Glu medium developed a neurotoxicity, expressed in the increase of LDH, NO andMDA, and the decrease of activity of SOD, as well as the development of morpho-logical injury. Ami (10-6, 10-7, 10-8 mol·L-1 ) signifi-cantly protected neurons against above demage.CONCLUSION: Ami can prevent rat cerebral neurons injury from the toxicity of Glu.
    Comparison of the effect of azone and menthol on the percutaneous ab-sorption of indomethacin in vitro
    ZHA Zhen-Zhong, WANG Hui, FENG Xiao-Long, XU Wei-Ming
    2002, 7(1):  27-29. 
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    AIM: To compare the permeation-en-hancing characters of menthol and azone on the model drug of indomethacin and to study the enhancing effect when the two agents were used in combination. METHODS: The transdermal test was conduced on the penetra-tion experiment apparatus of isolated skin.The cumulate penetrated amount, penetrating rate, stable flux and lag time were calculated upon the concentrations.RESULTS: After adding the penetration enhancer, the pen-etrating rate of indomethacin increased remarkably. It was 6.21,4.91 and 6. 92 times of that of the controls respec-tively. When used in combination, the two penetration enhancers increased much more the penetrating rate than being used separately (P <0.01).The penetration en-hancer could shorten the lag time of absorption of in-domethacin evidently. The lag time in the menthol group was shortened more evidently than that in the combined group (P <0.01).Azone had little effect on the stable flux of absorption of indomethacin, while menthol de-creased it. When the two penetration enhancerswere used in combination, distinct enhancing effect was observed.It was 2.78 and 1.38 times of that of separate agents re-spectively. CONCLUSIONS: Menthol and azone can re-markably enhance the percutaneous absorption of in-domethacin in vitro, and the enhancing effect is stron-gened when they are used in combination.
    Effects of salvia miltiorrhiza injection on acute myocardial ischemia and hemorheology models of rat
    WANG Chang-Sheng, YANG Jie-Ren, GUI Chang-Qing, DING Bai-Ping, SONG Jian-Guo
    2002, 7(1):  30-32. 
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    AIM: To investigate effects of salvia mil-tiorrhiza injection on acute myocardial ischemia and hemorheology. METHODS: The acute myocardial is-chemia model and blood stasis model were established with high-dose adrenaline subcutaneous injection and be-ing socked in ice-water. The effect of salvia miltiorrhiza injection on the electrocardiogram J-point and T-ware of acute myocardial ischemia and the hemorheology of rat blood stasis model were observed. RESULTS: As com-pared with model groups, middle and high dose groups of salvia miltiorrhiza injection could obviously inhibit the rising of J-point and T-wave of the ischemic electrocardio-gram, all dose groups of salviamiltiorrhiza injection could prevent the ascending of blood viscosity and fibrinogen and hematocrit. CONCLUSION: salvia miltiorrhiza in-jection can effectively decrease blood viscosity and im-prove circulatation of coronary artery, and protect is-chemic myocardium.
    Effect of notoginsenosiole on Ca2+, excitory amino acid content in rat brain of cerebral is chemia and reperfusion
    LIU Jia-Hui, JI Feng-Yun, WANG Ting, XIE Xue-Dong, YAO Bin
    2002, 7(1):  33-34. 
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    Effects of compound Liuyi decoction and its components on the function of immune cells in Xuexu mice
    YUAN Yue, WUMing-Yu, SUN Rui-Yuan
    2002, 7(1):  35-36. 
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    Effect of Nujin pills and capsule on the activity of rat' s uterus in vitro and rabbit' s uterus in vivo
    BI Ming, CHEN Qi, WU Wei-Qing, FENG Guang-Wu, LIU Yuan-Bo
    2002, 7(1):  37-40. 
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    Cardiovascular pharmacodynamics of the Riyuedan capsule in rats
    DUAN Yan-Nan, LIU Yuan-Bo
    2002, 7(1):  41-42. 
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    Investigation on the tolerance of ibandronate by a single intravenous infu-sion
    WANG Rui, FANG Yi, WANG Zhong-Xiao, XUE Jun-Feng, WANG Ya-Qin, ZHU Man, CHEN Lei, WANG Pei-Lan, ZHANG Xin-Gang, LI Xin-Hua
    2002, 7(1):  43-47. 
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    AIM: To evaluate the safety and toler-ance of ibandronate in Chinese healthy volunteers. METHODS: The trial protocol wasdesigned according to the Good Clinical Practice(GCP). After physical exami-nation and laboratory tests were performed, 36 healthy volunteers were divided randomly into 6 dose groups, in-cluding 1 mg, 2 mg, 3 mg, 4 mg, 5 mg and 6 mg, with 6 subjects in each group(3 male and 3 female). Clinical symptoms, vital signs, routine blood tests, routine urine tests, hepatic function, renal function, blood elec-trolytes, electrocardiogram, and electroencephalogram were observed or examined before and after a single intra-venous infusion of ibandronate.RESULTS: After single intravenous infusion doses of 1 -6 mg, the vital signs, clinical symptoms and laboratory testswere all in the nor-mal range, but there were some slight ADRs concerned with the drug, such as hypophosphataemia, increased body temperature, perspiring, pain of bone or muscle and hypocalcaemia. But the ADRs were found vanishing in one or two weeks.CONCLUSION: Single intravenous infusion (up to 6 mg) of domestic ibandronate in 36 chi-nese healthy volunteers is safe and tolerable.
    Determination of etheofazine (EDMTP)and its metabolite in human plas-ma by reversed-phase HPLC
    FU Liang-Qing, LIANG Yue-Qin, SUN Cheng-Chun, LI Jie, WU De-Zheng
    2002, 7(1):  48-50. 
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    AIM: To develop a method to determin- ing etheofazine(EDMTP) and its metabolite etheotriazene (EDMTP-Ⅱ) by HPLC in human plasma.METHODS: Human plasma samples containing etheofazine(EDMTP) and its metabolite EDMTP-Ⅱ after addition of internal standard (IS) , was extracted with ethylacetate and sepa- rated in a reversed-phase ODS column, and the detection was achieved at 345 nm by ultra-violet (UV).RESULTS: The limit of detection was 0.05 mg·L-1 for both etheofazine(EDMTP) and its metabolite EDMTP-Ⅱ. No potential interference was found.The method provided recoveries up to 81.42%-104.67%and accepted coef- ficients of variation were found for both within-run (<9.95%) and day-to-day (<9.14%) assays.CONCLUSION: This method is rapid, sensitive and simple for studying the pharmacokinetics of EDMTP and its metabolite EDMTP-Ⅱ .
    Urapidil and nitroglycerine for the control of cardiovascular responses to tracheal intubation/extubation in patients with essential hypertension
    CHAI Xiao-Qing, CHEN Kun-Zhou
    2002, 7(1):  51-53. 
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    AIM: To study the effectiveness of ura-pidil and nitroglycerine on controlling the cardiovascular responses to tracheal intubation/extubation in patients with essential hypertension.METHODS: 45 patients with essential hypertension undergoing general anesthesia were divided randomly into control (C, without depres-sor, n =15), urapidil (U, 0.5 mg·kg-1, n =15), and nitroglycerine (N, 1 μg·kg-1, n =15) groups.The SBP, DBP, MAP, HR and RPP were measured during intubation and extubation and at the induction of anesthe-sia and the end of operation respectively. RESULTS: The SBP, DBP, MAP, HR and RPP increased markedly (P <0.01) in group C, but SBP, DBP, and MAP re-mained stable in group U and group N;compared with group C, there were significant difference in the same pe-riods during tracheal intubaton/extubation respectively (P <0.01). The raising levels of HR, RPP in group U and groupN were lower significantly than those in group C (P <0.01). CONCLUSION: Urapidil and nitroglycerine can reduce the cardiovascular responses to tracheal intu-bation/extubation effectively, and be helpful in keeping the hemodynamic stability, especially in patients with es-sential hypertension.
    Linear relationship between pharmacokinetic parameters and doses about potassium clavulanic acid and amoxicillin
    XIA Chun-Hua, JIANG Min, XIONG Yu-Qing
    2002, 7(1):  54-56. 
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    AIM: To study the linear relationship be-tween pharmacokinetic parameters and doses about potas-sium clavulanic acid (CAV)and amoxicillin (AMX). METHODS: 15 healthy male volunteers were randomly divided into 5 dose-groups.The plasma concentration of CAV and AMX was determined by high performance liq-uid chromatography (HPLC)method.The pharmacokinet-ic parameters obtained with 3p97 soft were regressed to corresponding dose. RESULTS: The regression equations of AUC and cmax to dose about CAV were Y =2.0895X +0.4438 (r =0.9915)and Y =0.9397X +0.1796 (r =0.9922), respectively. The regression equations of AUC and cmax to dose about AMX were Y =4.8795X + 2.4794(r =0.9988)and Y =1.7276X +1.4832 (r = 0.9935), respectively. CONCLUSION: There is good linear relationship between pharmacokinetic parameters and doses about CAV and AMX.
    Pharmacokinetics andbioequivalenceof sustained-released tablet ofnefopam
    WANG Shao-Hua, YU Bao-Dong, CHEN An-Jin, CHU Xiao, JIANG Xin-Dao, ZHAO Mei-Ling, YAN Mei-Xing
    2002, 7(1):  57-59. 
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    AIM: To verify the bioequivalence be-tween sustained-released tablet of nepopam and normal one.METHODS: 18 volunteers were randomly devided into two groups.Double-periodical crossed design was used, and poly-dose of nefopam was administered to 18 volunteers following single-dose after one-week interval. The concentration of nefopam hydrochloride in serum was determinated by HPLC, and the related parameters came out through 3p97 programme. RESULTS: In the single-dose test the drug concentration of sustained-released tablet maitained 2040 mg·L-1 for 10 h, cmax was (45.8 ±15.7) mg·L-1, tpeak was (3.4±0.8) h, and the cor-responding parameters of normal tablet were over 20 mg·L-1 for 7.5 h, (72.7±26.0) mg·L-1, and (1.6 ±0.6) h.The AUC was (363.4 ±107.1) and (374.8 ±125.7) mg·h·L-1 respectively, and F was (1.02 ± 0.25). In the poly-dose test the cmax of sustained-re-leased and normal one was (31.50±12.65) and (33.68 ±10.51) mg·L-1, cmin was (13.4±4.4) and (10.9± 5.4) mg·L-1, tpeak was (2.6 ±0. 6) and (1.22 ± 0.46) h, and FI was (0.77±0.26) and (1.04±0.18) respectively. CONCLUSION: The sustained-released tablet is credible and the two types of tablet are equieffec-tive in AUC.
    Detection of homozygous P16 gene deletion in Non-Hodgkin' s Lymphoma by semiquantitative multiplex polymerase reaction and it' s clinical signifi-cance
    JI Zhao-Ning, LIU Guo-Qing, XU Dou-Rong, HONG Wen-De
    2002, 7(1):  60-62. 
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    AIM: To investigate the possible relation-shop between Non-Hodgkin's lymphoma and homozygous deletion of P16 gene. METHODS: Fifty one Non-Hodgkin's lymphoma specimens were examined for ho-mozygous deletion of P16 gene by multiplex polymerase chain reaction.RESULTS: Of 51 Non-Hodgkin's lym-phoma specimens, 9 (17.65 %) showed homozygous deletion of P16 gene.There was a significant difference between the low malignancy NHL, and the high malignan-cy NHL (P <0.05) in homozygous deletion of P16 gene. CONCLUSIONS: Deletion of P16 gene might contribute to the progression of Non-Hodgkin' s lymphoma and may be one of the important parameters in estimating the prog-nosis of patients with NHL.
    Clinical effects of Juzao Pills on the recrudes-cent and transmigration of breast cancer after surgery
    XIANG Li-Ping, OUYANG Hen, XIAO Yi-Liang
    2002, 7(1):  63-64. 
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    Treatment of 52 cases with diabetic derebral infarction by prostaglandin E1
    WANG De-Bao, LU Deng-Cai, ZHANG Feng-Mei
    2002, 7(1):  65-66. 
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    Clinical study of valsartan in the treatment of hypertension with left ventricular hypertrophy
    SHI Hai-Feng, HUA Shou-Ming, JIN Heng
    2002, 7(1):  67-68. 
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    Effect of Chaigetongmai oral liquor on hyper-lipidemia
    WANG Zhi-Hua, SHEN Qing-Liang, XU Jin-Zhen, LIU Qing-Jun
    2002, 7(1):  69-70. 
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    Clinical study of cisplatin ointment in treat-ment of psoriasis
    YAN Jun, QU Pong-Chen, WANG Xiao-Dong
    2002, 7(1):  73-74. 
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    Effects of Naokangtai capsule on sixty-two cas-es parkinson' s disease
    CAO Zi-Cheng, LI Feng-Lian, ZHANG Yao-Sheng
    2002, 7(1):  75-76. 
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    Effect of lamivudine on the quota of liver fi-brosis with cirrhosis infected by HBV
    CHEN Hua-Zhong, ZHANG Jian-Bo
    2002, 7(1):  77-77. 
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    Effects of Xindakang tablet in the treatment of 98 cas-es with cornonary heart disease
    WU Yu-Fang, JIN Li-Ping, DING Guo-Yin
    2002, 7(1):  79-79. 
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    Effets of interferon α-2b on serum hpaluronic acid in patients with hypatitis B and hypatitis C
    LI Yi-Ling, WANG Feng-Ha, LI Qing-Yang
    2002, 7(1):  80-80. 
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    Methods in analysis of the dynamics of drug interaction and its software CoDrug
    ZHENG Qing-Shan, SUN Rui-Yuan
    2002, 7(1):  81-85. 
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    In clinical and experimental therapeutics, the quantitative analysis of drug interaction will supply a tool for optimizing and evaluating a combination in the study of compound drug, the design of combination drug therapy, and the evaluation of traditional medicine formu-lae. This paper listed the systematic methods of the quan-titative analysis, including the weighted modification method for optimizing constituents, doses and ratio in combination, the parameter method and the reflection method for dynamic analysis of drug interaction, and a comprehensive method for multiple response indexes.The software CoDrug about these methods also was introduced.
    Progress in the pharmacodynamics of antibi-otics
    REN Shao-Hua, HU Hua-Chen
    2002, 7(1):  86-89. 
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    Progress in treatment of cancer by somato-statin and its resemblances
    TU Jiu-Sheng, WU Pei, XIA Xiang-Huo, RUI Jing
    2002, 7(1):  90-93. 
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    Current researches on traditional Chinese medicine of anti-hypertension
    LI Li, WANG Qian-Mao
    2002, 7(1):  94-96. 
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