【摘要】 为研制适于猪的药物代谢动力学研究的传染病模型，取长白×杜洛克杂种猪１６头（体重３２．Ｏ±０．７ｋｇ），每猪皮下接种纯净猪链球菌（Ｃ＿（７４－４１）型）１２．５亿个活菌，复制出典型的亚急性型猪链球菌病。动物经感染后ｌｄ体温持续升高１．５～２．０℃．血浆总蛋白含量开始持续降低（Ｐ＜０．０１），血清肌酐浓度则开始升高（Ｐ＜０．０５）。感染后２．５ｄ，磺溴酞的消除半衰期和给药后１５ｍｉｎ的滞留率均下降（Ｐ＜０．０５），而酚磺酞的消除和分布参数无显著变化（Ｐ＞０．０５）。第５天，血中红细胞和血红蛋白总量减少（Ｐ＜０．０５和０．０１），但血细胞的沉降速率加快（Ｐ＜０．０１）。与此同时，异烟肼的消除率和乙酰化率下降（Ｐ＜０．０５），消除半衰期延长（Ｐ＜０．０１）。上述结果表明，该疾病模型以高热、贫血、血浆胶透压下降、肝乙酰化和肾小球滤过功能障碍为特征。这些特征将影响药物在体内的分布和血浆蛋白结合率，改变药物及其代谢物从体内消除的速度和程度，进而影响药物的疗效或毒副作用。由于该模型具有猪的一般传染病所共有的临床和病理特征，复制的方法可靠且具有可重复性，它对探讨药物在传染病猪体内的动力学规律，揭示疾病对药动学的影响机理和指导?更多还原

【Abstract】 s In order to prepare a contagious disease model for pharmacokinetic studies inswine,sixteen hybrid pigs(32.0±0.7kg b.w.) were used to develop a typical subacutestreptococcosis suum by inoculating subcutaneously l.25 billion of pure living Streptoco-ccus suis(type C74-41)to each animal.Just at the lst day after inoculation,the tempe-rature of the infected animals was 1.5 to 2.0℃ higher continuously than uninfected,which was followed by the decrease of the total amounts of plasma protein(p<0.0l)and the increase of the concentrations of serum creatinine(P<0.05). At the 2.5thday,the residence rate of bromsulphalein at l5 min after intravenous bolus injectionwere reduced and its half-life of elimination was shortened(P<0.05). However,therewas no significant changes of the elimination and distribution of phenolsulfonphthaleinadministered intravenously between before and after injection(P<0.05).At the 5thday,the amounts of both erythrocytes and haemoglobin in the blood were decreased(P<0.05 & 0.01, respectively),but the erythrocyte sedimentation rate was faster thannormal(P<0.05).Meanwhile,the clearance and acetyl-metabolite proportion of isoniazidwere reduced(P<0.05),and in consequence,its elimination half-life was prolonged(P<0.01).The results buggest that the developed disease model is characterized byfever, anemia,the decrease of colloid osmotic pressure in the blood,the reduction ofacetylation capacity in the liver and the disfunction of glomerular fiIteration in thekidney.Such features could affect the distribution and the plasma protein-binding of adrug in the body,determine the elimination speed and extent of the drug and itsmetabolites from the animals,and then change the therapeutic or toxic side-effects ofthe drug.The present model has theoretical and practical significances for the pharma-cologists to investigate the disposition of drugs in infected swine,demonstrate theprinciples of the effects of contagious diseases on pharmacokinetics of drugs and guideveterinarians how to use drugs reasonably in clinics,because it has the same generalnatures as other infectious deseases of swine clinically and pathologically,and also itedevelopment is reliable and repetitious under the same experimental conditions.更多还原