药临床前毒理学评价.ppt

Index--Urinalysis尿液外观Colorandappearance比重SpecificgravitypH值pHvalue尿糖Glucose尿蛋白Protein尿胆红素Bilirubin尿胆原Urobilinogen酮体Ketones潜血Blood白细胞WBC亚硝酸盐Nitrite镜检*MicroscopyofcentrifugeddepositIndex--Pathology称重并计算系数心脏heart肝脏liver脾脏spleen肺脏lung肾脏kidneys脑brain肾上腺adrenals胸腺thymus睾丸testes附睾epididymides子宫uterus卵巢ovariescalculateorganweightsrelativetobodyweight,pairedorgansweightogetherIndex--Pathology病检脏器组织脑（大脑、小脑、脑干）脊髓（颈、胸、腰段）垂体胸腺甲状腺甲状旁腺食管唾液腺胃小肠和大肠肝脏胆囊*肾脏肾上腺脾脏胰腺气管肺Index--Pathology病检脏器组织主动脉心脏附睾睾丸卵巢子宫前列腺乳腺坐骨神经膀胱眼（发现异常时）*视神经*给药局部骨髓淋巴结（包括给药局部淋巴结、肠系膜淋巴结）Index--Pathologyheartliverspleenlungkidneybrainadrenalspancreasstomachduodenumjejunumileumcoloncecum（盲）pituitarythymusspinalcordprostatetestesepididymidesuterusovariesopticnerveinjectionsiteboneandmarrowurinarybladderlymphnodes(mesenteric,local)thyroidparathyroidlobes脏器取材样式（SOP)肺脏脑肝脏01肾脏02膀胱03心脏04肺05脾脏胸腺06甲状腺07气管08脑垂体09胃10切片中组织排列和方向Index—ECG,Eye大动物长期毒性必须做ECG观察指标：心率、P波电压、P-R间期、R波电压、QRS时间、ST段、T波电压和Q-T间期Observation:1/3～1/2animal,2～6wLatetoxicreactionandreversibilityItems:sameastreatmentperiodRecovery能反映动态变化发现有阳性指标应加大观察密度大动物ECGⅡ导联，给药前、给药期间、停药及恢复期均要检测一般行为、食量每天观察记录大动物生理指标每半月一次大鼠体重每周一次测试次数WesternChineseRecombinant3～4times≥2timesantibody≤6m(rat)9m(dog)Toxicreaction:properties,degree,dose-toxicityrelationship,initiatingtime，peaktime,lastedtime,latereactiontoxicity,accumulatingtoxi-city,toleranceObservations0102Frequencyoflab.investigationsrat=3mrat6mNon-rodentlastad.