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

Table of Content

    Volume 12 Issue 7
    26 July 2007
    MDR-and CYP3A4-mediated drug-herbal interactions
    MAO Xiao-qin, XIE Hai-tang, ZHOU Hong-hao
    2007, 12(7):  728-734. 
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    According to recent epidemiological reports more and more people, both healthy and ill, use all kinds of Chinese herbal medicine during their lifetime.As the increasing combined usage of Chinese herbal medicine with prescription drugs, it draws lots of attentions on the therapeutic activity due to possible drug-herb interaction. It is known that P-glycoprotein (P-gp)together with cytochrome P450 3A4 (CYP3A4)leads to a highly efficient barrier for many orally absorbed drugs.Meanwhile, more than 50% of the clinical drugs are metabolized by CYP3A4 or transported by P-gp.Hence, more attention should be paid to MDR-and CYP3A4-mediated drug-herbal interactions.This survey discusses the key-factors of drug-herbal interaction as well.
    Function of melatonin in human retina
    HUANG Wen-li, TANG Min, FAN Ying
    2007, 12(7):  735-738. 
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    Melatonin(MLT) is an indolakylamine with many physiological functions, and retina is one of its natural secretory portions.Melatonin plays an important role in retina, including regulating diurnal rhythmicity of retina, protecting against oxidation and apoptosis, regulating retinal neural network and so on.Researches on mechanism of action may appreciate ophthalmological clinical application of melatonin.So this article will review on its synthesis, metabolism, acceptors distribution and function in retina.
    Effects of gamma-aminobutyric acid on diabetic etiopathogenesis
    ZHOU Ji-yin, ZHOU Shi-wen
    2007, 12(7):  739-742. 
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    Diabetes mellitus is a frequent endocrine disorder disease and its etiopathogenesis is still not completely known, which is caused by several factors.In recent years gamma-aminobutyric acid was believed to have something to do with the formation of diabetes mellitus. The glutamic acid decarboxylase, which is one of the earlier autoantigens causing diabetes mellitus, is the synthetase inhibitor of gamma-aminobutyric acid.The relationship of gamma-aminobutyric acid, islets of langerhans and the central nervous system in diabetes mellitus was reviewed in this paper.
    Physiological functions of poly(ADP-ribose) polymerase and potential clinical applications of its inhibitors
    WANG Hui-yuan, SUN Hong-bin
    2007, 12(7):  743-747. 
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    Poly(ADP-ribose)polymerases(PARP)is one of the most important enzymes in human body.It plays an vital role in chromatin relaxation, signal transduction, DNA damage repair and apoptosis.Its over-activation induces necrosis and pathological processes.Therefore, inhibition of PARP may provide potential therapeutic approaches to treatment of a variety of diseases.This review presents an overview of PARP's functions and potential clinical applications of PARP inhibitors.
    LC-MS/MS-based measurement of danshen phenolic acids in plasma
    CHEN Ping, LU Tong,WU Bo-ying, DU Fei-fei, GAO Xiu-mei, ZHANG Bo-li, LI Chuan
    2007, 12(7):  748-755. 
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    AIM: To develop sensetive and specific LC-MS/MS-based methods for measurement of plasma tanshinol (TSN), protocatechualdehyde (PCA), and salvianolic acid A, B, and D (SAA, SAB, and SAD)in supporting the pharmacokinetic evaluation of Cardiotonic pills, a standardized danshen-containing cardiovascular phytomedicine. METHODS: Electrospray ionization (ESI)patterns and efficiency of the analytes, along with their fragmentation, were investigated to achieve sensitive ESI-MS/MS detection.Sample preparation was also studied to effectively recover the analytes from plasma.Meanwhile, chromatographic conditions were optimized to avoid matrix component interference on analyte ESI-detection. The newly developed analytical methods were evaluated with respect to accuracy, precison, selectivity, sensitivity, and stability. RESULTS: The negative ion ESI gave a high ionization efficiency for the analytes.The precursor-to-product ion pairs m z 197→135, 136→108, 493→295, 717→519, and 417→197 were used for sensitive and specific SRM of TSN, PCA, SAA, SAB, and SAD, repectively.For the best measurement of the analytes, two methods were developed, i.e., one for determination of plasma TSN and the other one for simultanious determination of plasma PCA, SAA, SAB, and SAD.The sample preparation for the two quantification methoids involved acidifying the plasma sample with HCl before EtOAc-based liquid-liquid extraction;the extraction efficiency was 57.7%-61.6% for TSN from plasma or 38.0%-58.9% for PCA、SAA、SAB, and SAD in parallel from plasma.Matrix-matched standard curves of the peak area of a given analytes versus the nominal plasma concentration were linear for concentrations of TSN between 2.7 ng/mL and 2 000.0 ng/mL, with a correlation coefficient 0.999 and a lower limit of quantification 2.7 ng/mL, while linear dynamic ranges for PCA, SAA, SAB, and SAD were 1.37 or 4.1-1000.0 ng/mL, with correlation coefficients>0.99 and lower limits of quantification 1.4 ng/mL for PCA and 4.1 ng/mL for SAA, SAB, and SAD.Both the quantification methods demonstrated a within-run assay accuracy and presion 90%-112% and 2.5%-15%, respectively and a between-run data 91%-110% and 0.7%-9.4%, respectively.Further, the applicability of the newly developed analytical methods was demonstrated in a pilot plasma pharmacokinetic study in a beagle dog receiving an intravenous dose of injectable extract from Cardiotonic pills. CONCLUSION: Sensetive and specific LC-MS/MS-based methods for measurement of plasma TSN and for measurement of plasma PCA, SAA, SAB, and SAD in parallel are developed and validated, which are applicable to pharmacokinetic evaluation of Cardiotonic pills.
    Effects of propofol on potassium currents in pulmonary artery smooth muscles of rats
    JIANG Yu-ge, XU long-he, ZHANG Hong
    2007, 12(7):  756-759. 
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    AIM: To investigate the effects of propofol on potassium currents in pulmonary artery smooth muscle cells of normotensive and hypertensive rats. METHODS: The effects of propofol on potassium currents in smooth muscle cells derived from normotensive and hypertensive rats pulmonary arteries were observed by patch clamp technique (whole cell recording) after application of the drug in the bath. RESULTS: The potassium current-voltage curves (I-V curves) of smooth muscle cells derived from normotensive and pulmonary hypertensive rats pulmonary arteries were up-ward shifted by propofol (50, 100 μmol/L).Compared with control group, within 5 minutes after application of the drug, the current amplitude could increase to (121±11)%, (113±5)% (P<0.01) and (126±5)%, (122±8)% (P<0.01) of initial current amplitude respectively. CONCLUSION: The out-ward potassium currents in smooth muscle cells derived from normotensive and pulmonary hypertensive rats could be increased by propofol.This may be one of the mechanisms that propofol can decrease pulmonary vascular tension and dilate pulmonary vessel.
    Effects of heparin on expression of leptin and transforming growth factor β1 in rat hepatic stellate cells
    CHEN Yi-ping, XU Zhi-wei, SHI Hai-fang, DI Jun-bo, CHEN Jun-ya, WANG Hong-jiao
    2007, 12(7):  760-762. 
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    AIM: To explore the effects of heparin on the expression of leptin and transforming growth factor β1 (TGF β1) in rat hepatic stellate cells(HSCs). METHODS: HSCs were divided as follows:heparin group Ⅰ(10 μg/mL), Ⅱ(100 μg/mL), Ⅲ(1 000 μg/mL), and control group.The incubation liquid was extracted after cultured 48 h and frosted in-20 ℃.Leptin and TGF β1 were detected by ELISA, the HSC proliferation was measured by MTT assay. RESULTS: The levels of leptin in heparin group Ⅱ, Ⅲ were significantly lower than that in control group(P<0.01).The level of TGF β1 and the mean absorbance in heparin groups were significantly lower than that in control group (P<0.01). CONCLUSION: Heparin can decrease expression of leptin and TGF β1 in HSCs and inhibit proliferation of HSCs.
    Protective effect of propofol on free radical induced cortex mitochondria injury in rats
    JIA Dong-lin, CHU Xiao-yu, ZHANG Li-ping
    2007, 12(7):  763-766. 
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    AIM: To evaluate the protective effects of propofol on oxidative injury of rat cortex mitochondria. METHODS: Lipid peroxidation was induced by ascorbic acid-Fe2+, the swelling of mitochondria and the decrease of membrane fluidity were induced by ascorbic acid-Fe2+ system.The fluidity of mitochondral membrane, content of malondialdehyde (MDA) in mitochondria and the swelling of mitochondria were measured. RESULTS: The swelling of mitochondria and the decrease of membrane fluidity induced by ascorbic acid-Fe2+ system were alleviated by propofol(P<0.05).30 μmol/L propofol could protect mitochondria from ascorbic acid-Fe2+ induced lipid peroxidation. CONCLUSION: Propofol can protect mitochondria from oxidative injury induced by ascorbic acid-Fe2+.
    Autologous bone marrow mesenchymal stem cell transplantation for acute myocardial infarction in pigs
    FANG Wu-wang, LIN bin-lai, ZHANG Sheng-xia, LIU Ling-ling, CHEN Shao-liang
    2007, 12(7):  767-772. 
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    AIM: The preclinical study was designed to test the feasibility and safety of autologous bone mesenchymal stem cell (MSC) transplantation by intracoronary injection in pigs with acute myocardiac infarction. METHODS: Coronary obstruction with balloon was used to produce acute myocardial infarction (AMI).Labeled MSCs were implanted by intracoronary injection.Four weeks later, single photon emission computed tomography was used to evaluate the relative infarct size.The myocardial ventricular systolic pressure (LVSP), left end-diastolic pressure (LVEDP), peak of pressure rise (LV+dp/dtmax) and peak rate of pressure fall (LV-dp/dtmin) were assessed by catheterization.Immunofluorescence was performed to evaluate MSC engrafment and differentiation. RESULTS: Compared with control group, heart function parameters were all improved in pigs receiving MSCs transplantation, including EF [(44.1±4.3)% vs (39.0±5.2)%, P<0.05] perfusion score [(30.0±5.3) vs (41.8±8.8), P<0.01], relative infarct size [(28.6±4.7)% vs (33.5±3.4)%, P<0.05], LVSP (87±9 mm Hg vs 78±4 mm Hg, P<0.05), LV+dp/dtmax [(1818±117) mm Hg/s vs (1611±115) mm Hg/s, P<0.01, 1 mm Hg=0.133 kPa], LV-dp/dtmin [(1801±89) mm Hg/s vs (1618±66) mm Hg/s, P<0.01] and LVEDP [(9.4±1.7) mm Hg vs (12.6±2.8) mm Hg, P<0.05].MSCs implanted in myocardium were stained positively for myosin heavy chain, connexin 43, smooth muscle actin and von Willebrand factor. CONCLUSION: These results demonstrate that transplantation of MSCs can improve cardiac function in AMI pig, and that the improvement might result from myocardial regeneration and angiogenesis by MSC differentiation.
    Effect of matrine on U937 cells and human umbilical vein endothelial cells proliferation
    YANG Ze-song, CHEN Jian-bin, MU Jun, GE Qun-fang, LU Qian-wei, LIAO Yang, HUANG Zong-gan
    2007, 12(7):  773-777. 
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    AIM: To observe the proliferative effects of matrine on U937 cells and human umbilical vein endothelial cells. METHODS: The effects of matrine on U937 cells and human umbilical vein endothelial cells proliferation were observed by morphology, MTT and cell cycle detection. RESULTS: U937 cells treated with matrine at the concentration of 0.2 mg/mL to 0.5 mg/mL for 24 h were inhibited proliferation in a time and dose-dependent manner detected by MTT (P<0.05 or P<0.01) and increased at the S stage (P<0.05 or P<0.01).The half-inhibition concentration (IC50) was 0.4 mg/mL in U937 cells compared with human umbilical vein endothelial cells (P>0.05).HUVECs treated with matrine at the concentration of 0.1 to 0.5 mg/mL for 48 h showed no effect on cell cycle (P>0.05). CONCLUSION: Matrine has an inhibited effect on U937 cells proliferation in a time and dose-dependent manner.
    Effect of anti-hypercoagulability state enzyme of agkistrodon venom on hepatocarcinoma and expresion of P53, C-MYC in mice
    ZHANG Zheng-ming, RUI Jing, CHAI Zhi-ming
    2007, 12(7):  778-781. 
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    AIM: To research the inhibitory effect of antihypercoagulability state enzyme(AHCSE) of agkistrodon venom on the hepatocarcinoma in Balb cmice bearing hepatocarcinoma (H22) strain in situ and its possible mechanisms. METHODS: Hepatic cancer H22 model in mice was established on axillary fossa (Balb c) subcutaneouly, to obtain post-passage carcino-tissue and raise on mice livers.All animals were divided into 4 groups, 10 mice each group:control group, low-AHCSE group(0.5 mg/kg), middle-AHCSE group(1.0 mg/kg) and high-AHCSE group(2.0 mg/kg).Different dosages of AHCSE were injected via vena caudalis every three days for three times.To explore therapic efficacy of different dosages of AHCSE on the basis of percent inhibition of neoplastic weight and positive cells of P53 and C-MYC. RESULTS: The experiment of aniso-dosage of AHCSE indicates, percent inhibition of tumor(PIT) was 35.57% in low-AHCSE group (0.5 mg/kg), the PIT in the middle-dosage group(1.0 mg/kg) was 50.38% and in high-AHCSE group (2.0 mg/kg) PIT was 53.89%.The expression of P53 protein was 64, 51 and 45 and the expression of CMYC protein was 46, 38 and 34 in the three dosages groups.Inhibitory effect on tumor was significantly inmiddle-AHCSE and high-AHCSE. CONCLUSION: AHCSE has the significantly inhibitory effect on tumor in dose dependent.AHCSE may inhibit the tumor via down regulation the expression of P53, C-MYC protein.
    Effects of 1-(3-fluorophenyl)-5-methyl-2-(1H) pyridone on hepatic stellate cells
    LI Ping, TAO Li-jian, HU Guo-ling, TAN De-ming
    2007, 12(7):  782-785. 
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    AIM: To explore the mechanism of 1-(3-fluorophenyl)-5-methyl-2-(1H) pyridone (FMP) against hepatic fibrosis. METHODS: The inhibitory effect of FMP on hepatic stellate cells(HSC) proliferation was observed by MTT, and the expression levels of collagen type I, III protein of HSC were detected by immunocytochemistry. RESULTS: HSC proliferation was decreased after incubation with FMP for 48 h at the dosage range from 200 μg/mL to 600 μg/mL compared with that in control group, and FMP could also significantly decrease the protein expression of collagen type I, III at the dosage of 200 μg/mL. CONCLUSION: FMP can inhibit the proliferation of HSC and decrease the expression of type Ⅰ, Ⅲ collagen, which are related to the mechanism of FMP treating hepatic fibrosis.
    Protection of atorvastatin on cardiac function following ischemia-reperfusion injury in rabbits
    ZHOU Yi, CHEN Man-hua, LIU Jin-hua, ZHANG Li-yun
    2007, 12(7):  786-789. 
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    AIM: To observe the effect of atorvastatin (ATV) on myocardial ischemia-reperfusion injury and the role of inducible nitric oxide synthase (iNOS). METHODS: The rabbits were randomly divided into control group, ATV group, ATV+S-Methylisothiourea sulfate (SMT) group, SMT group.All rabbits were subjected to 40 min ischemia and 240 min reperfusion.The hemodynamic variables, CK-MB, LDH-1 and nitric oxide synthase were detected after reperfusion. RESULTS: LVDP and+dp/dtmax decreased by 24.6% and 35.3%respectively following ischemia-reperfusion.Pre-treated by ATV (10 mg·kg-1·d-1) for three days, LVDP and+dp/dtmax decreased by 21.7% and 41.3%, CK-MB and LDH-1 by 31.4% and 19.1% and iNOS increased to 102.6%.The reduction of LVDP and+dp/dtmax, CKMB, LDH-1 and iNOS in ATV+SMT group was no statistically significant with those in control group. CONCLUSION: ATV pretreatment protected myocardial ischemia-reperfusion injury by upregulating iNOS.
    Anti-bradycardic effect of Ganfu granule in rats
    WANG Di-sheng, CEN De-yi, CHEN Zhi-wu
    2007, 12(7):  790-793. 
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    AIM: To study the anti-bradycardic effect of ganfu granule (Gan) in rats. METHODS: The bradycardic model in rats was induced by propranolol (Pro) or acetylcholine (ACh).The content of malonaldehyde (MDA) was measured by TBA method, the Green method was used to determine the content of nitric oxide (NO). RESULTS: Gan(30, 90, 270mg/kg) significantly inhibited the Pro-induced decrease of heart rate in rats, and shortened the time of rat bradycardia induced by ACh. Gan 30, 90, 270mg/kg markedly increased the NO content, and reduced the MDA content in rat myocardium. CONCLUSION: Gan has the obvious anti-bradycardic effect via increasing NO reduction, while attenuating oxygen free radical damage.
    Effects of total flavones of epimedium through different administration pathways on experimental myocardial ischemia
    WANG Qiu-juan, PAN Zhi-wei, YANG Juan, YUE Pan, KONG Ling-yi
    2007, 12(7):  794-799. 
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    AIM: To observe the effects of total flavones of epimedium on experimental myocardial ischemia through intravenous injection and gastroenter-administration pathway. METHODS: Acute myocardial ischemia model of mice was induced by subcutaneous injection (s.c.)of isoproterenol (20 mg/kg).The effects of the injection of total flavones of epimedium(PSTFE, i.v.) and total flavones of epimedium(TFE, i.g.)on the survival time of mice were observed.Acute myocardial ischemia model was induced by ligating coronary artery in anaesthetized dogs. Then epicardium electrocardiogram (EECG)was measured, and creatine kinase (CK), lactic acid (LD), superoxide dismutase (SOD)and malonaldehyde (MDA)in the serum, cardiac infarction area were determined respectively. RESULTS: PSTFE (i.v.)and TFE (i.g.)could both significantly increase the survival time of acute myocardial ischemia mice(P<0.01).PSTFE (iv gtt)and TFE (i.d.)could obviously reduce the value of △N-ST and △∑-ST, decrease the infarction area, notably decrease the levels of CK, LD and MDA in the serum, and distinctly increase the level of SOD(P<0.05). CONCLUSION: Total flavones of epimedium through intravenous injection and gastroenteradministration pathway have significantly protective effects on experimental myocardial ischemia.
    Influence of hawthorn leaves flavonoids on electrocardiogram, nitrogen monoxidum and malondia1dehyde of myocardial ischemia reperfusion injury in rats
    MIN Qing, BAI Yu-ting, ZHANG Zhi, SHI Lu-yi
    2007, 12(7):  800-803. 
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    AIM: To study the influence of hawthorn leaves flavonoids on electrocardiogram (ECG), NO and malondialdehyde (MDA) of myocardial ischemia reperfusion injury in rats. METHODS: Myocardial ischemic reperfusion injury models were established by occluding the left anterior descending branch of coronary artery for 30 min and removing the ligation later to reperfuse for 60 min in vivo.Different dosages of hawthorn leaves flavonoids(12.5, 25.0, 50.0 mg/kg) were administered by i.p.10 min before the onset of ischemia.ECG was observed continuously and ST segments were measured.The concentrations of NO in blood serum were detected and the contents of MDA in myocardium were assaied in the same time. RESULTS: ST segments of ECG were relieved significantly treated with hawthorn leaves flavonoids (12.5, 25.0, 50.0 mg/kg).NO concentrations were increased and MDA contents were decreased significantly in the different dosages groups compared with control group. CONCLUSION: Hawthorn leaves flavonoids has protective effects on myocardial ischemia reperfusion injury.The effect were possibly attributed to increasing concentrations of NO and anti-lipid peroxidation.
    Effects of water extract of purslane herb on protecting telomere length of senile mouse
    HUANG Hao, YU Nan-cai, LIU Qian, YI Yan-dong, MA Wei
    2007, 12(7):  804-807. 
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    AIM: To investigate the protective effect of water extract of Purslane herb on telomere length in senile mouse. METHODS: The senile mouse models induced by D-gal were divided randomly into five groups: normal control group, 3 experimental groups and model group.Animals were fed with normal diet in control and model groups and with normal diet plus 2.5, 5.0, 10.0 g/mL water extract of Purslane herb respectively in experimental groups.The telomerase activation of senile mouse brain was detected by PCR-TRAP-ELISA.The lengths of telomeric restriction fragments (TRFs) were detected by southern-blot assay.The mRNA and protein expression levels of c-myc and p53 gene were detected by real-time fluorescence quantitative RT-PCR and western blot. RESULTS: The telomerase activity in senile mouse brain was significantly increased after treated with water extract of purslane herb.The telomere length in senile mouse brain was improved by water extract of purslane herb.The expression of p53 gene was decreased and c-myc gene was not activated. CONCLUSION: Water extract of purslane herb has possibly delayed the aging of senile mouse through inhibiting the p53 gene expression and activating the telomerase to protect the length of telomere in brain.
    Study of mathematical models of scales for evaluating efficacy in symptomatology
    LV Ying-hua, XU Ling, YANG Juan, HE Ying-chun, LIU Hong-xia, SUN Rui-yuan, ZHENG Qingshan
    2007, 12(7):  808-813. 
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    AIM: To develop a symptom scale for evaluating efficacy of the multi-enzyme combination capsule in treatment of patients with dyspepsia symptoms be caused digestive enzyme insufficient. METHODS: The symptom score is always related to the incidence rate (f requency), the importance (evaluated by experts) and the serious degree (light, moderate and serious) in a measuring scale, and a mathematical model was proposed to calculate the weight factor and its scores for each symptom in the scale.In an example of the multi-enzyme combination capsule in treatment of patients with chemical dyspepsia, the efficacy was analyzed based on the symptom scales with this approach.The scale was evaluated with the reliability, the validity, the responsibility to change, and the simulation. RESULTS: Six symptoms (epigastric distention, easy satiety, the degression of appetite, belches, counter-sour and nausea) were selected as indices, and their weight factors and grades were calculated in score scales.Some evaluations demonstrated that the approach showed a better feasibility, uniformity, and responsibility to change.The sample size (100-2 000) and the flutter (10%) of the importance and the frequency yielded a little effect on total scores in simulation. CONCLUSION: This is a reliable approach in developing a scale of symptomatology for evaluating efficacy of drugs.
    Study on tolerance of subcutaneous injection in single dose of recombinated human glucagon-like peptide-1 in Chinese healthy volunteers
    WANG Rui, PEI Fei, CHAI Dong, FANG Yi, ZHENG Zhuan-jie, SHANG Wen, LIANG Bei-bei, DONG Tao, LI Cong-ran, AN Mao-mao
    2007, 12(7):  814-818. 
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    AIM: To estimate the safety and tolerance of recombinated human glucagon-like peptide-1(rh-GLP-1) (7-36) after subcutaneous injection of single dose of the drug in Chinese healthy volunteers. METHODS: The protocol was designed according to GCP and approved by ethics committee.All volunteers signed the informed consent.The volunteers were 18-45 years old and divided into 7 dosage groups.The clinical and laboratory tests were observed in order to evaluate the safety and tolerance of rhGLP-1 (7-36). RESULTS: All laboratory and clinical indexes of the subjects were within the normal range and qualifications were equilibrate before administration of the drug, so they were comparable.After administration of rhGLP-1 (7-36), the incidence of adverse events (nausea, vomiting) exceeded 50% in 0.30 mg group, so only 24 cases in 4 groups (0.10-0.30 mg) joined the phasa I clinical trial.After administration of the drug, the significant changes in laboratory tests were not seen, but adverse reactions such as dizziness, nausea and emesia in 10 cases (15 times) were found which might be related to the drug.They could be tolerable, were temporary response, and disappeared one hour after the administration.The ADR occurred mainly in the 0.25 mg and 0.30 mg groups (7 of 12 subjects), while the ADR in the low-dose groups (0.10, 0.20 mg) were only found for 3 cases.There were 10 cases with dizziness and nausea and 5 emesia among 15 ADR.There were no serious adverse events during the clinical trial. CONCLUSION: rhGLP-1(7-36) is safe and tolerable in Chinese healthy volunteers when the single dose under 0.20 mg is subcutaneously injected, and the most tolerable dose is 0.20 mg.When the dose is up to 0.25 mg or 0.30 mg, the incidence of ADR is higher.The mechanisms for ADR of the nausea and vomiting will be studied in future.
    Determination of rosuvastatin calcium in human plasma by LC-MS/MS and its clinical pharmacokinetics in Chinese healthy volunteers
    LI Chun-ying, ZHANG Yu-ying, DING Li
    2007, 12(7):  819-823. 
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    AIM: To establish a rapid and sensitive LC-MS/MS method for the analysis of rosuvastatin calcium in plasma and study the pharmacokinetics of rosuvastatin on China healthy volunteers. METHODS: Plasma samples containing rosuvastatin calcium and fluvastatin sodium were extracted with liquid-liquid extraction, followed by liquid chromatographic separation and on-line MS/MS using turboionspray ionization as an interface detection by the multi-reaction monitoring. RESULTS: The limit of quantitation of method for rosuvastatin calcium was 0.03 ng/mL, the calibration curves in plasma were linear over the range of 0.03 to 60 ng/mL and within-batch and between-batch variation over the range were less than 10%. CONCLUSION: The method is shown to be accurate and convenient, and suitable for pharmacokinetic studies of rosuvastatin calcium.
    Pharmacokinetics and relative bioavailability of cyclovirobuxine D orally disintegrating tablets in healthy volunteers
    YU Peng, DI Bin, LIU Wen-ying, GAO Shu, DONG Hai-jun, SUN Di, RAO Jin-hua, XU Jihua
    2007, 12(7):  824-831. 
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    AIM: To study the relative bioavailability and bioequivalence of cyclovirobuxine D orally disintegrating tablets and cyclovirobuxine D tablets in healthy volunteers. METHODS: 2 mg of cyclovirobuxine D orally disintegrating tablets and cyclovirobuxine D tablets was given to 22 healthy volunteers in a randomized crossover study. The concentration of cyclovirobuxine D in plasma was determined by LC/MS/MS after a solid phase extraction (SPE).The pharmacokinetic parameters were calculated and the bioavailability and bioequivalence of two formulations were evaluated by DAS 2.0 software. RESULTS: After a single dose, the pharmacokinetic parameters of cyclovirobuxine D and reference were as follows:Cmax, (121±55) and (122±52) ng/L;tmax, (10±7) and (12±8) h;AUC0-120 h, (4398±1656) and (4524±1760) ng·L-1·h;AUC0→inf, (5292±2034) and (5440±2446) ng·L-1·h, respectively.The 90% confidential interval of Cmaxof cyclovirobuxine D orally disintegrating tablet was 82.7%-117.3%.The 90% confidential interval of AUC0-120 and AUC0→inf of cyclovirobuxine D orally disintegrating tablet were 83.9%-112.9% and 83.4%-117.6%, respectively. CONCLUSION: The relative bioavailability of cyclovirbuxine D orally disintegrating tablets to cyclovirobuxine D tablets is (97.7±14.7)%.The results of the statistic analysis show that the test and reference formulations are bioequivalent.
    Efficacy of adefovir dipivoxil in treating patients with hepatitis B resistant to lamivudine
    LI Wen-li, WU Shi-pin
    2007, 12(7):  832-834. 
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    AIM: To evaluate the efficacy and safety of adefovir dipivoxil in treating patients with hepatitis B resistant to lamivudine. METHODS: 68 patients with hepatitis B resistant to lamivudine were administered 10 mg adefovir dipivoxil orally daily for over 1 years.The serum HBV-DNA levels were measured by quantitative PCR and liver function test, HBeAg anti-HBe and safety assessments were also performed at 0, 12, 24, 52 weeks after treatment. RESULTS: After 12, 24, 52 weeks of treatment, the mean HBV-DNA levels were reduced by 1.6 lg copies/mL (t=10.10, P<0.01), 2.9 lg copies/mL (t=13.01, P<0.01) and 4.5 lg copies/mL(t=14.08, P<0.01).The normalization rates of ALT levels were 19.12%, 48.53% and 70.59%.The HBeAg loss rates were 0%, 19.44%and 47.22%.The HBV-DNA undetectable rates were 4.41%, 19.12% and 54.41% respectively. CONCLUSION: Adefovir dipivoxil is effective and safe for treating chronic hepatitis B patients with lamivudine resistance.
    Clinical efficacy and safety evaluation of Jianweiyuyangpian in treatment of 314 patients with peptic ulcer
    LIANG Xiao-qing, DING Hong-ming, LI Ai-guo, CHANG Sheng, WANG Xian-guo, HE Jun, ZHAO Yi
    2007, 12(7):  835-837. 
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    AIM: To evaluate the clinical efficacy and safety of Jianweiyuyangpian in the treatment of 314 patients with peptic ulcer. METHODS: 446 patients with peptic ulcerwere randomly divided into two groups of treatment group and control group.314 patients in treatment group were administered with Jianweiyuyangpian orally and 132 patients in control group with ranitidine capsules for 4 weeks. RESULTS: After treating for 4 weeks the ulcer cure rate, efficacy rate, six month recurance rate, pain relief rate and pain disappearance rate of treatment group were 59.87%, 91.40%, 12.24%, 93.00% and 79.33% respectively, while those of control group were 58.33%, 89.39%, 14.04%, 88.46% and 72.30% respectively.The differences between two groups were not significant (P>0.05).Both of the two groups had no adverse event. CONCLUSION: Jianweiyuyangpian is a safe and effective drug for treating peptic ulcer.
    Effects of repeated administration of fentanyl on fentanyl-induced coughing
    ZHANG Zhi-yong, HUANG Yu-guang, ZHOU You, REN Hong-zhi, LUO Ai-lun
    2007, 12(7):  838-840. 
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    AIM: To observe the effects of repeated intravenous administration of fentanyl 1 μg/kg on fentanylinduced coughing during anesthesia induction. METHODS: 300 patients with ASA Ⅰor Ⅱ for elective procedures, received an intravenous injection of fentanyl 1 μg/kg via a peripheral cannula prior to anesthesia induction.The patients who experienced cough were randomly divided into two equal groups according to the interval of repeated administration:group 2 min received the same dosage of fentanyl 2 min later and group 5 min was administrated the same dosage of fentanyl 5 min later.The occurrence of cough was recorded.The level of cough was graded. RESULTS: The incidence of fentanyl-induced cough in the first administration was 18% (54/300).After repeated administration, the occurance of cough in group 2 min (0%, 0/27) was lower than that in group 5 min (40.7%, 11/27) (P<0.01).There was significant difference on the severity between two groups (P<0.01). CONCLUSION: The incidence of fentanyl-induced coughing was significantly decreased after repeated administration of fentanyl 1 μg/kg during anesthesia induction, but the incidence of cough may be increased with the prolonging of the dosing interval.