抗生素作為獸藥經(jīng)常使用�？咕幠退幮陨仙托滦涂股氐娜狈κ且粋�(gè)全球性的危機(jī),因此迫切需要克服這一問(wèn)題。不恰當(dāng)?shù)目股剡x擇、群體治療和不合理的劑量是產(chǎn)生上述問(wèn)題的主要原因。一種減少藥物抗菌性的方法是優(yōu)化劑量方案。PK/PD模型被應(yīng)用于這一領(lǐng)域許多年。PK/PD模型可描述藥物、病原和機(jī)體三者之間的關(guān)系。正確使用現(xiàn)代的PK/PD模型可以優(yōu)化藥物用量,從而降低毒性和減少耐藥性的出現(xiàn)。本研究的目的是基于體外、體內(nèi)、健康和疾病模型觀察PK/PD在獸醫(yī)現(xiàn)有的狀態(tài)和應(yīng)用。頭孢喹肟在豬血漿中的藥代動(dòng)力學(xué)研究:頭孢喹肟血漿樣品經(jīng)HLB萃取后進(jìn)行HPLC分離和檢測(cè),HPLC包括反相C18色譜柱,流動(dòng)相為0.1%甲酸溶液乙腈（90:10,v/v）。校準(zhǔn)曲線的線性范圍為0.01-5μg/mL,檢測(cè)限（LOD）和定量限（LOQ）分別為0.01和0.04μg/mL,低、中、高三個(gè)添加濃度的血漿樣品中,頭孢喹肟的回收率為73.4%,78.33%,和77%。日內(nèi)和日間相對(duì)標(biāo)準(zhǔn)偏差均小于15%。頭孢喹肟在-700C穩(wěn)定存在超過(guò)3個(gè)月,在40C能穩(wěn)定存在超過(guò)24個(gè)小時(shí)。本方法被成功地應(yīng)用于牛的藥代動(dòng)力學(xué)研究。肌注后,平均... 

【文章來(lái)源】：華中農(nóng)業(yè)大學(xué)湖北省 211工程院校 教育部直屬院校

【文章頁(yè)數(shù)】：130 頁(yè)

【學(xué)位級(jí)別】：博士

【文章目錄】：
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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