头孢喹肟对牛败血症病原金黄色葡萄球菌药动学/药效学同步关系研究

发布时间：2022-01-10 06:03

　　抗生素作为兽药经常使用。抗菌药耐药性上升和新型抗生素的缺乏是一个全球性的危机,因此迫切需要克服这一问题。不恰当的抗生素选择、群体治疗和不合理的剂量是产生上述问题的主要原因。一种减少药物抗菌性的方法是优化剂量方案。PK/PD模型被应用于这一领域许多年。PK/PD模型可描述药物、病原和机体三者之间的关系。正确使用现代的PK/PD模型可以优化药物用量,从而降低毒性和减少耐药性的出现。本研究的目的是基于体外、体内、健康和疾病模型观察PK/PD在兽医现有的状态和应用。头孢喹肟在猪血浆中的药代动力学研究:头孢喹肟血浆样品经HLB萃取后进行HPLC分离和检测,HPLC包括反相C18色谱柱,流动相为0.1%甲酸溶液乙腈（90:10,v/v）。校准曲线的线性范围为0.01-5μg/mL,检测限（LOD）和定量限（LOQ）分别为0.01和0.04μg/mL,低、中、高三个添加浓度的血浆样品中,头孢喹肟的回收率为73.4%,78.33%,和77%。日内和日间相对标准偏差均小于15%。头孢喹肟在-700C稳定存在超过3个月,在40C能稳定存在超过24个小时。本方法被成功地应用于牛的药代动力学研究。肌注后,平均... 

【文章来源】：华中农业大学湖北省 211工程院校 教育部直属院校

【文章页数】：130 页

【学位级别】：博士

【文章目录】：
摘要
ABSTRACT
PUBLISHED WORK
ABBREVIATION AND SYMBOLS
1. INTRODUCTION
    1.1 INFECTIOUS DISEASES
    1.2 SEPTICEMIA
    1.3 RATIONAL THERAPY FOR SEPTICEMIA
    1.4 PHARMACOKINETICS STUDY OF CEFQUINOME
    1.5 PHARMACODYNAMICS STUDY
    1.6 PHARMACOKINETIC AND PHARMACODYNAMICS MODEL
    1.7 PK/PD INDEX
    1.8 CONCENTRATION DEPENDENT
    1.9 TIME DEPENDENT
    1.10 PK/PD MATHEMATICAL MODELLING
    1.11 PK/PD AND DOSE
    1.12 OBJECTIVES
2. MATERIALS AND METHODS
    2.1 MATERIALS
        2.1.1 Reagents, chemicals and drugs
        2.1.2 Scientific Software
        2.1.3 Apparatus
        2.1.4 Standard and stock solution formation
        2.1.5 Animals
    2.2 DEVELOPMENT OF HPLC-UV METHOD FOR QUANTIFICATION OF CEFQUINOME
        2.2.1 HPLC CONDITION
        2.2.2 SAMPLE PREPARATION PROCEDURE
        2.2.3 Method validation
            2.2.3.1 Selectivity
            2.2.3.2 Limit of quantification and detection
            2.2.3.3 Calibration curve
            2.2.3.4 Precision and accuracy
            2.2.3.5 Stability
    2.3 MICROBIOLOGY: PHARMACODYNAMICS OF CEFQUINOME
        2.3.1 Bacterial strains
        2.3.2 Bacterial Recovery
        2.3.3 Growth curve
        2.3.4 Determination of MIC, MBC, MPC and PAE
    2.4 IN-VIVO STUDY
        2.4.1 Sample collection after Intravenous administration
        2.4.2 Sample collection after Intramuscular administration
        2.4.3 Pharmacokinetic analysis
    2.5 PHARMACOKINETICS AND PHARMACODYNAMICS INTEGRATION
        2.5.1 In vitro and Ex-vivo bacterial killing curves
        2.5.2 Pharmacodynamics analysis, PK-PD integration and PK-PD modelinganalysis
3. RESULTS
    3.1 BIO ANALYSIS AND ITS APPLICATION
        3.1.1 Method Validation
            3.1.1.1 Selectivity and calibration curve
            3.1.1.2 Limit of detection (LOD) and Limit of quantification (LOQ)
            3.1.1.3 Recovery, precision and accuracy
            3.1.1.4 Stability
        3.1.2 Pharmacokinetics of Cefquinome
            3.1.2.1 Pharmacokinetics study after Intravenous administration
            3.1.2.2 Pharmacokinetics study after Intramuscular administration
    3.2 MICROBIOLOGY
        3.2.1 Growth curve of staphylococcus aureus
        3.2.2 MIC, MBC, MPC and PAE of Cefquinome against staphylococcus aureusstrains
        3.2.3 WT MIC distribution and ECV
    3.3 IN-VITRO AND EX-VIVO INHIBITION CURVE
    3.4 PHARMACOKINETICS AND PHARMACODYNAMICS MODELLING
        3.4.1 PK/PD integration
        3.4.2 PK/PD modelling
        3.4.3 Estimation of Dose
4. DISCUSSION AND CONCLUSIONS
    4.1 CHROMATOGRAPHIC CONDITION AND SAMPLE PREPARATION
    4.2 CONNECTION WITH OTHER PREPARATION TECHNIQUES
    4.3 METHOD PERFORMANCE CHARACTERISTICS
    4.4 PK/PD INTEGRATION
    4.5 CONCLUSION
5. SUMMARY
6. FUTURE WORKS
7. A REVIEW
    7.1 GENERAL PRINCIPLES AND METHODOLOGY OF PK/PD
    7.2 PK/PD INDEX
    7.3 TIME DEPENDENT
    7.4 PK/PD AND CLINICAL BREAKPOINT
    7.5 PK/PD AND DOSE
    7.6 PK/PD MATHEMATICAL MODELLING
    7.7 PK/PD AND ANTIMICROBIAL RESISTANCE
    7.8 PK/PD AND DEVELOPMENT OF NEW FORMULATIONS AND DRUGS FORANIMAL USES
    7.9 CONCLUSION
BIBLIOGRAPHY
ACKNOWLEDGMENT
DEDICATION
APPENDIX



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