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Synergistic effect of combining paeonol and cisplatin on apoptotic induction of human hepatoma cell lines

Acta Pharmacologica Sinica 2007年第6期28卷 869-878页

作者： Shu-ping XU~2,Guo-ping SUN~(4,5),Yu-xian SHEN~2,Wan-ren PENG~4,Hua WANG~3,Wei WEI~2~2 Institute of Clinical Pharmacology,anhui medical university,Key Laboratory of Anti-inflammatory and Immunological Pharmacology,Key Laboratory of Research and Development of Chinese Medicine,hefei 230032,china ~3 department of oncology,Provincial hospital ofanhui,hefei 230001,china ~4 department of oncology,the first affiliated hospital of anhui medical university,hefei 23.022,china Institute of Clinical Pharmacology Anhui Medical University Key Laboratory of Anti-inflammatory and Immunological Pharmacology Key Laboratory of Research and Development of Chinese Medicine Hefei China department of oncology The First Affiliated Hospital of Anhui Medical University Hefei China department of oncology Provincial Hospital of Anhui Hefei China

Aim:To investigate whether paeonol （Pae） has synergistic effects with cisplatin（CDDP） on the growth-inhibition and apoptosis-induction of human hepatomacell lines HepG2and ***:The cytotoxic effect of drugswas measured by 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyl-tetrazolium *** coefficient of drug interaction was used to analyze the nature of *** changes were observed by acridine orange fluo-rescence *** cycle and the apoptosis rate were detected by ***-2 and Bax expression were assayed by ***:Pae or CDDP had antiproliferative effect on the 2 cell linesin a dose-dependent manner,with different sensitivities to ***,a synergistic inhibitory effect on the viability of the 2 cell lineswas observed after treatment with a combination of Pae （15.63,31.25,and 62.5mg/L） with various concentrations of *** study showed typical mor-phological changes of apoptosis if the cells were exposed to the two agents for24 *** apoptotic rate of the cells with combination treatment was signifi-cantly higher than that of cells treated with Pae or CDDP *** expressionof Bcl-2 decreased and that of Bax increased in the treated groups,especially inthe combination group,with the ratio of Bcl-2/Bax decreasing ***,a combination of Pae with CDDP resulted in a stronger S phasearrest,compared with Pae or CDDP ***:Pae,in combinationwith CDDP,had a significantly synergistic growth-inhibitory and apoptosis-in-ducing effect on the 2 human hepatoma cell lines,which may be useful inhepatoma treatment.

关键词： paeonol cisplatin drug interaction human hepatoma cell line apoptosis cell cycle

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Melatonin ameliorates experimental hepatic fibrosis induced by carbon tetrachloride in rats

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World Journal of Gastroenterology 2009年第12期15卷 1452-1458页

作者： Ru-Tao Hong,department of Geriatrics Medicine,the first affiliated hospital of anhui medical university,hefei 23.022,anhui Province,china Ru-Tao Hong,Jian-Ming Xu,Qiao Mei,department of Gastroenterology,the first affiliated hospital of anhui medical university,hefei 23.022,anhui Province,china The Key Laboratory of Digestive Diseases of anhui Province,hefei 23.022,anhui Province,china department of Geriatrics Medicine The First Affiliated Hospital of Anhui Medical University Hefei 230022 Anhui Province China.

AIM:To investigate the protective effects of melatonin on carbon tetrachloride(CCl4)-induced hepatic fibrosis in experimental ***:All rats were randomly divided into normal control group,model control group treated with CCl4 for 12 wk,CCl4+NAC group treated with CCl4+NAC(100 mg/kg,i.p.)for 12 wk,CCl4+MEL-1 group treated with CCl4+melatonin(2.5 mg/kg)for 12 wk,CCl4+MEL-2 group treated with CCl4+ melatonin(5.0 mg/kg)for 12 wk,and CCl4+MEL-3 group treated with CCl4+melatonin(10 mg/kg).Rats in the treatment groups were injected subcutaneously with sterile CCl4(3 mL/kg,body weight)in a ratio of 2:3 with olive oil twice a *** in normal control group received hypodermic injection of olive oil at the same dose and frequency as those in treatment *** the end of experiment,rats in each group were anesthetized and *** and eosin(HE)staining and Van Gieson staining were used to examine changes in liver *** activities of alanine aminotransferase(ALT),aspartate aminotransferase(AST)and protein concentration weremeasured with routine laboratory methods using an ***(HYP)content in liver and malondialdehyde(MDA)and glutathione peroxidase(GPx)levels in liver homogenates were assayed by *** hyaluronic acid(HA),laminin(LN),and procollagenⅢN-terminal peptide(PⅢNP)were determined by ***:Pathologic grading showed that the fibrogenesis was much less severe in CCl4+MEL3 group than in model control group(u=2.172,P4-induced hepatic fibrotic *** serum levels of ALT and AST were markedly lower in CCl4+MEL treatment groups(5,10 mg/kg)than in model control group(ALT:286.23 ±121.91 U/L vs 201.15±101.16 U/L and 178.67 ±103.14 U/L,P=0.028,P=0.007;AST:431.00 ±166.35 U/L vs 321.23±162.48 U/L and 292.42 ±126.23 U/L,P=0.043,P=0.013).Similarly,the serum laminin(LN)and hyaluronic acid(HA)levels and hydroxyproli

关键词： Melatonin Hepatic fibrosis Oxidativestress Hyaluronic acid Laminin Malondialdehyde Glutathione peroxidase

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No association between IRF3 polymorphism and susceptibility to hepatitis B virus infection in Chinese patients

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World Journal of Gastroenterology 2012年第4期18卷 388-392页

作者： Fang Yan,Feng Lv,Xu Li,Hua-Fa Yin,department of Infectious Diseases,the first affiliated hospital of anhui medical university,hefei 230032,anhui Province,china Yu-Feng Gao,department of Hepatopathy,The Second affiliated hospital of anhui medical university,hefei 230601,anhui Province,china Tian-Chen Zhang,department of Epidemiology and Biostatistics,School of Public Health,anhui medical university,hefei 230032,anhui Province,china department of Infectious Diseases The First Affiliated Hospital of Anhui Medical University Hefei 230032 Anhui Province China.

AIM:To investigate the association between three tag single nucleotide polymorphisms (tagSNPs) in inter-feron regulatory factors (IRF3) and the genetic suscep-tibility to chronic hepatitis B virus (HBV) ***:We performed a case-control study of 985 Chinese cases of chronic HBV infection and 294 self-limiting HBV-infected individuals as *** tagSNPs in IRF3 (rs10415576,rs2304204,rs2304206) were genotyped with the Multiplex SNaPshot *** genotype and allele frequencies were calculatedand ***:The three SNPs showed no significant geno-type/allele associations with chronic HBV *** allele P values were:rs10415576,P=0.0908,odds ratio (OR) [95% confidence interval (CI)]=1.1798 (0.9740-1.4291);rs2304204,P=0.5959,OR (95% CI)=1.0597 (0.8552-1.3133);rs2304206,P=0.8372,OR (95% CI)=1.0250 (0.8097-1.2976).Overall genotype P values were:rs10415576,P=0.2106;rs2304204,P=0.8458;rs2304206,P=*** were no statisti-cally significant differences between patients with chron-ic HBV infection and *** generated by these three SNPs were also not significantly different between the two ***:The three tagSNPs of IRF3 are not asso-ciated with HBV infection in the Han Chinese population.

关键词： Chronic hepatitis B virus infection Interferon regulatory factors tag single nucleotide polymorphisms Genetic susceptibility Haplotype

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Cyclooxygenase-2 polymorphisms and susceptibility to gastric carcinoma: A meta-analysis

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World Journal of Gastroenterology 2010年第43期16卷 5510-5517页

作者： Jia-Li Liu, Zhen-Ning Wang, department of Surgical oncology and General Surgery, the first affiliated hospital of china medical university, Shenyang 110001, Liaoning Province, china Yuan Liang, department of oncology, the Shengjing affiliated hospital of china medical university, Shenyang 110001, Liaoning Province, china Xin Zhou, department of Obstetrics and Gynecology, the Shengjing affiliated hospital of china medical university, Shenyang 110001, Liaoning Province, china Li-Li Xing, department of oncology, the Fourth affiliated hospital of china medical university, Shenyang 110032, Liaoning Province, china department of Surgical oncology and General Surgery the First Affiliated Hospital of China Medical University Shenyang 110001 Liaoning Province China.

AIM: To investigate the association of the cyclooxygenases-2 (COX-2) polymorphisms and susceptibility to gastric cancer (GC) by means of meta-analysis. METHODS: Publications addressing the association between polymorphisms of COX-2 and susceptibility to GC were selected from the MEDLINE, EMBASE and CBMdisc databases. Data was extracted from the studies by 2 independent reviewers. The meta-analyses were performed by RevMan 5.0.23. From these data, odds ratio (OR) with 95% confidence interval (CI) was ***: Ten studies were retrieved reporting a total of 11 COX-2 polymorphisms. Carriers of -765C, -1195A, -1290G, *2430T alleles and *429TT genotype revealed increased risk for GC (OR = 1.71, 95% CI: 1.01-2.90, P = 0.05; OR = 1.58, 95% CI: 1.05-2.38, P = 0.03; OR = 1.55, 95% CI: 1.01-2.39, P = 0.05; OR = 2.62, 95% CI: 1.20-5.73, P = 0.02 and OR = 0.74, 95% CI: 0.59-0.95, P = 0.02, respectively). CONCLUSION: The -765C, -1195A, -1290G, *2430T alleles and *429TT genotype of COX-2 polymorphisms were determined a significant association with susceptibility to GC.

关键词： Cyclooxygenases-2 Gastric cancer Polymorphisms Susceptibility Meta-analysis

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Evidence-based expert consensus on clinical management of safety of Bruton’s tyrosine kinase inhibitors(2024)

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Chinese Journal of Cancer Research 2024年第3期36卷 240-256页

作者： Zaiwei Song Dan Jiang Lingling Yu Yixuan Chen Daobin Zhou Yue Li Depei Wu Lingli Zhang Liyan Miao Jun Ma Jun Zhu Hongmei Jing Rongsheng Zhao the Steering Committee,the Consensus Panel and the Evidence Synthesis Group Evidence-based Pharmacy Professional Committee of Chinese Pharmaceutical Association(CPA) hospital Pharmacy Professional Committee of Chinese Pharmaceutical Association(CPA) Division of Therapeutic Drug Monitoring of Chinese Pharmacological Society(CPS) Expert Committee on Lymphoma of Chinese Society of Clinical oncology(CSCO) Expert Committee on Leukemia of Chinese Society of Clinical oncology(CSCO) Society of Integrative Cardio-oncology of china Anti-Cancer Association(CACA) Chinese Society of Hematology of Chinese medical Association(CMA) hospital Pharmacy Professional Committee of Cross-Straits Medicine Exchange Association(SMEA) department of Pharmacy Peking University Third HospitalBeijing 100191China Institute for Drug Evaluation Peking University Health Science CenterBeijing 100191China Therapeutic Drug Monitoring and Clinical Toxicology Center Peking UniversityBeijing 100191China department of Pharmacy Administration and Clinical Pharmacy School of Pharmaceutical SciencesPeking UniversityBeijing 100191China department of Hematology Peking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100005China department of Cardiology the First Affiliated HospitalHarbin Medical UniversityHarbin 150001China department of Hematology the First Affiliated Hospital of Soochow UniversitySuzhou 215006China department of Pharmacy Evidence-based Pharmacy CenterWest China Second HospitalSichuan UniversityChengdu 610041China department of Pharmacy the First Affiliated Hospital of Soochow UniversitySuzhou 215006China department of Hematology and oncology Harbin Institute of Hematology and OncologyHarbin 150010China Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Department of LymphomaPeking University Cancer Hospital&InstituteBeijing 100142China department of Hematology Peking University Third HospitalBeijing 100191China 不详

Bruton’s tyrosine kinase inhibitors(BTKis)have revolutionized the treatment of B-cell ***,safety issues related to the use of BTKis may hinder treatment continuity and further affect clinical efficacy.A comprehensive and systematic expert consensus from a pharmacological perspective is lacking for safety issues associated with BTKi treatment.A multidisciplinary consensus working group was established,comprising 35 members from the fields of hematology,cardiovascular disease,cardio-oncology,clinical pharmacy,and evidencebased *** evidence-based expert consensus was formulated using an evidence-based approach and the Delphi *** Joanna Briggs Institute Critical Appraisal(JBI)tool and Grading of Recommendations Assessment,Development,and Evaluation(GRADE)approach were used to rate the quality of evidence and grade the strength of recommendations,*** consensus provides practical recommendations for BTKis medication based on nine aspects within three domains,including the management of common adverse drug events such as bleeding,cardiovascular events,and hematological toxicity,as well as the management of drug-drug interactions and guidance for special *** multidisciplinary expert consensus could contribute to promoting a multi-dimensional,comprehensive and standardized management of BTKis.

关键词： Consensus BTK inhibitors safety adverse drug events drug-drug interactions

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Alterations in circadian rhythms of melaton in and cortisol in patients with bronchial asthma

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Acta Pharmacologica Sinica 2004年第5期25卷 109-114页

作者： Guang-he FEI2,3, Rong-yu LIU3,4, Zhi-hong ZHANG3, Jiang-ning ZHOU2,32School of Life Science, university of Science and Technology of china, hefei 230026, china 3Pulmonary department, first affiliated hospital, anhui medical university, hefei 23.022, china School of Life Science University of Science and Technology of China Hefei 230026 Pulmonary department First Affiliated Hospital Anhui Medical University Hefei 230022 Pulmonary department First Affiliated Hospital Anhui Medical University Hefei 230026

AIM: To investigate the possible relationships between alterations in circadian rhythm of melatonin, cortisol andbronchial asthma. METHODS: Salivary melatonin and cortisol were measured simultaneously by radioimmunoas-say in 10 mild intermittent or persistent patients, 11 moderate-to-severe persistent asthma patients, and 15 controlsubjects. Twelve salivary samples were collected in a series during a 24-h period in each subject. RESULTS: Theresults showed overall lower levels of salivary melatonin in asthma patients compared with control subject(P4-h mean level of salivary cortisol was greatly lower and the acrophase was markedly delayedin patients with mild intermittent or persistent asthma (P<0.01) and moderate-to-severe persistent asthma (P<0.05, P<0.01) compared with control subject. CONCLUSION: Disordered circadian rhythms of salivary melato-nin and cortisol were found in asthma patients, which may be involved in the pathogenesis of bronchial asthma.

关键词： melatonin asthma circadian rhythm glucocorticoids human saliva

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Pharmacodynamic effects and kinetic disposition of rabeprazole in relation to CYP2C19 genotype in healthy Chinese subjects

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Acta Pharmacologica Sinica 2005年第3期26卷 384-388页

作者： Yong-mei HU~(2,3) Jian-ming XU~(3,5) Qiao MEI~3 Xin-hua XU~3 Shu-yun XU~42 anhui Geriatric Institute 3 department of Gastroenterology,first affiliated hospital of anhui medical university 4 Clinical Pharmacology Institute,anhui medical university,hefei 23.022,china anhui Geriatric Institute Hefei 230022 China department of Gastroenterology First Affiliated Hospital of Anhui Medical University Hefei 230022 China Clinical Pharmacology Institute Anhui Medical University Hefei 230022 China

Aim:To investigate whether the pharmacodynamics and pharmacokinetics ofrabeprazole are dependent on CYP2C19 genotype status in healthy Chinese ***:The CYP2C19 genotype status of healthy Chinese Hart volun-teers was determined using the polymerase chain reaction-restriction fragmentlength polymorphism *** healthy subjects volunteered to participatein the *** were seven homozygous extensive metabolizers （homEM）,sixheterozygous extensive metabolizers （hetEM）,and seven poor metabolizers （PM）.All subjects were Helicobactor pylori-negative,which was determined by sero-logy and13C-urea breath *** （20 mg） was taken orally once daily inthe morning for 8 days,and intragastric pH values were monitored for 24 h byDigitrapper pH after day 1 （single dose） and day 8 （repeated dose）.Meanwhile,blood samples were collected at various time-points for 24 h after *** serum concentrations of rabeprazole were measured using high-performanceliquid ***:The mean area under the curve （AUC） values forrabeprazole differed among the three different genotype groups,with a relativeratio of 1.0,1.3,and 1.8 after a single dose and 1.0,1.1,and 1.7 after repeated dosesin the homEM,hetEM,and PM groups,*** AUC values forrabeprazole after a single dose and after repeated doses were significantly differ-ent between the homEM and PM groups,but not between the homEM and hetEMor hetEM and PM *** significant differences in intragastric pH median,pH>4 total time,and pH>4 time percentage of 24 h,were observed among the threedifferent genotype groups after a single dose or after repeated doses of ***:In healthy Chinese Hart subjects,the pharmacokinetics of rabeprazoleare dependent on a certain degree on CYP2C19 genotype status;however,theacid-inhibitory efficacy of rabeprazole is not influenced significantly by CYP2C 19genetic polymorphism.

关键词： polymorphism(genetics) pharmacokinetics pharmacodynamics rabeprazole

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Circulating Adhesion Molecules in Patients with Keshan Disease and Their Relationship with Coxsackie B Virus Infection

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Journal of Huazhong university of Science and Technology(medical Sciences) 2009年第2期29卷 173-176页

作者：李从圣牛小麟雷聪 department of Emergency the Third Affiliated Hospital of Anhui Medical University and the First People's Hospital of Hefei department of Cardiology the Second Affiliated Hospital of Xi'an Jiaotong University

This study determined the levels of serum soluble intercellular adhesion molecule-1 （sI-CAM-l） and soluble vascular cell adhesion molecular-1 （sVCAM-1） in patients with different types of Keshan disease （KD）, examined the relationship between Coxsackie B virus-specific IgM antibody （CBV-IgM） and slCAM-1 or sVCAM-1 in KD patients, and investigated the role of these adhesion molecules in the pathogenesis of KD and their clinical implications. The levels of serum slCAM-1, sVCAM-1 and CBV-IgM were measured by using enzyme-linked immunosorbent assay in 22 patients with chronic Keshan disease （CKD）, 27 with latent Keshan disease （LKD） and 28 healthy controis. The subjects in different groups were adjusted for sex and age. Echocardiography was adopted to determine left ventricular ejection fraction （LVEF） in 22 patients with CKD. The results showed that CKD patients had significantly higher levels of slCAM-1 and sVCAM-1 than LKD patients and healthy controls （P〈0.01 for all）. And there was significant difference in the levels of the 2 adhesion molecules between LKD patients and healthy controls （P〈0.05）. A negative correlation was found between LVEF and slCAM-1 or sVCAM-1 in CKD patients. The percentage of CBV-specific IgM positive individuals in KD patients was significantly higher than that of healthy controls. In CVB-specific IgM positive patients, the levels of serum slCAM-1 and sVCAM-1 were significantly greater than those in CBV-specific IgM negative counterpart. It was concluded that the increase in the levels of slCAM-1 and sVCAM-1 suggests the progression of inflammation in KD. slCAM-1 and sVCAM-1 can promote the development of myocardial pathology and lead to poor myocardial function. The increased serum slCAM-1 and sVCAM-1 in KD patients may be related to CBV infection.

关键词： Keshan disease soluble intercellular adhesion molecule-l soluble vascular cell adhesion molecular-1 cardiac function Coxsackie B virus

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Oncofetal antigen glypican-3 as a promising early diagnostic marker for hepatocellular carcinoma

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Hepatobiliary & Pancreatic Diseases International 2011年第3期10卷 289-294页

作者： Research Center of Clinical Medicine,affiliated hospital of Nantong university,Nantong 226001,china (Yao M,Yao DF,Qiu LW,Wu W,Sai WL,Yang JL and Zhang HJ) department of oncology,Yancheng first People’s hospital,Yancheng 224001,china (Bian YZ) department of oncology,Second affiliated hospital,Nanjing medical university,Nanjing 210011,china (Zhang CG) Research Center of Clinical Medicine Affiliated Hospital of Nantong University Nantong 226001 China department of oncology Yancheng First People's Hospital Yancheng 224001 China department of oncology Second Affiliated Hospital Nanjing Medical University Nanjing 210011 China

BACKGROUND:Hepatocellular carcinoma (HCC) is characterized by a multi-cause,multi-stage and multi-focus process of tumor *** prognosis is poor and early diagnosis is of utmost *** study was undertaken to investigate the dynamic expression of oncofetal antigen glypican-3 (GPC-3) and GPC-3 mRNA in hepatocarcinogenesis and to explore their early diagnostic value for ***:A hepatoma model was induced in male Sprague-Dawley rats with 0.05% 2-fluorenylacetamide and confirmed by hematoxylin and eosin staining and gamma-glutamyltransferase (GGT) *** RNA was purified and transcribed into cDNA by reverse *** of the GPC-3 gene were amplified by nested RT-PCR,and confirmed by ***-3 was analyzed by immunohistochemistry,Western blotting or ***:Positive GPC-3 expression showed as brown granule-like staining localized in the *** examination of hepatocytes revealed three morphological stages of granule-like degeneration,atypical hyperplasia (precancerous),and cancer formation,with a progressive increase of liver total RNA and GGT *** incidence of liver GPC-3 mRNA and GPC-3,and serum GPC-3 was 100%,100% and 77.8% in the HCC group,100%,100%,and 66.7% in the precancerous group,83.3%,83.3%,and 38.9% in the degeneration group,and no expression in the liver or blood of the control group,*** was a positive correlation between liver GPC-3 mRNA and total RNA level (r=0.475,P4,P<0.001).CONCLUSION:Abnormal oncofetal antigen GPC-3 and GPC-3 mRNA expression in hepatocarcinogenesis may be promising molecular markers for early diagnosis of HCC.

关键词： hepatocellular carcinoma glypican-3 immunohistochemistry nested RT-PCR

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Influence of age and sex on pharmacodynamics of propofol in neurosurgical patients: model development

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Acta Pharmacologica Sinica 2006年第5期27卷 629-634页

作者： Yu-hong L1~(2,5) Fu-sheng WU~3 Jian-guo XU~4 ~2department of Anesthesiology,~3department of Surgical oncology,first affiliated hospital,Zhejiang university College of Medicine,Hangzhou 310003,china ~4department of Anesthesiology,Nanjing Jinling hospital,Nanjing 210002,china department of Anesthesiology First Affiliated Hospital Zhejiang University College of Medicine Hangzhou China department of Surgical oncology First Affiliated Hospital Zhejiang University College of Medicine Hangzhou China department of Anesthesiology Nanjing Jinling Hospital Nanjing China

Aim:To determine propofol concentration in the cerebral spinal fluid （CSF） ofneurosurgical patients and carry out a preliminary population ***:Twenty-seven elective neurosurgical patients （12 men and 15women） aged 17-74 years received propofol in a bolus dose of 2 mg/kg for 5 minand an infusion of 10 mg/kg per h for 5 *** CSF samples were drawn andassayed for propofol *** bispectral index （BIS） was used to mea-sure the drug *** data were analyzed first with the Excel software package,then pharmacodynamics modeling was performed using the NONMEM ***:The CSF concentration was related to the drug effect withlinear and sigmoid *** parameters for the linear addictive modelwere a= 1.11 and b=*** parameters for the linear exponential model were a=1.05 and b=*** parameters for the sigmoid Emaxmodel were Emax=119,EC50=53.6ng/mL,and N=*** the covariates of age,weight and sex wereconsidered,the parameters of models,objective function,the standard error of themean and the prediction error were not ***:Linear additive,linear exponential and sigmoid Emaxmodels can be used to describe the pharmaco-dynamics of propofol with respect to the concentration in *** this smallpopulation,age （17-74 years）,weight （47-98kg） and sex did not influence any ofthe pharmacodynamic parameters of *** verify these preliminary results,a larger study population is required.

关键词： propofol cerebrospinal fluid age factors sex factors pharmcodynamics

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