【作者】 方星星；

【导师】 张道波； 李健；

【作者基本信息】 中国海洋大学 ， 水产养殖， 2003， 硕士

【摘要】 本文分为两个部分，第一部分研究了22℃C±3℃和16℃±2℃水温条件下，多次口服给药后，复方新诺明（磺胺甲（口恶）唑SMZ／甲氧苄啶TMP=5／1）在花鲈的肌肉、血液、肝脏、肾脏四种组织中的残留和消除规律，并比较了不同温度下残留和消除规律的差别。第二部分研究了22.5℃±1℃水温条件下，以10mg／kg的剂量肌肉注射给药，恩诺沙星及其活性代谢物环丙沙星在中国对虾肌肉、血液、肝胰脏三种组织内的代谢情况，并设计出了合理的给药方案。各组织中药物浓度由高效液相色谱法测得。以上研究在国内均属首次。 研究结果表明：与TMP相比，SMZ在花鲈体内残留量较小，且消除较快。以22℃±3℃下肌肉中的残留情况为例，停药一天后SMZ和TMP在花鲈肌肉组织内的残留量分别为9.4和30.1μg／ml；消除半衰期T_1/2β分别为0.37d和1.98d。温度对SMZ和TMP在花鲈体内的吸收和消除均有影响，温度对于吸收的影响主要体现于TMP，22℃±3℃和16℃±2℃温度下，停药一天后TMP在肌肉、血液、肝脏、肾脏四种组织中的浓度分别为30.1，8.47，18.8，100.9μg／ml和12.9，5.6，8.27，23.2μg／ml，数据显示较高温度下，TMP在花鲈体内的吸收率较高；温度对SMZ的吸收率则无明显影响。温度对SMZ和TMP在花鲈组织内的消除速度的影响可从下列数据看出：22℃±3℃水温条件下，SMZ和TMP在肌肉、血液、肝脏、肾脏四种组织中的T_1/2β分别为0.37，0.47，0.72，0.48d和1.98，2.09，1.63，5.53d；16℃±2℃下的分别为0.72，0.95，1.90，1.11d和3.48，3.92，3.43，7.8d。说明两种药物在花鲈组织内的消除速度随温度的升高而加快，并且，SMZ的消除速度受温度影响更明显。综合两种药物在鱼体内的残留情况，建议花鲈在16℃和22℃水温条件下口服复方新诺明的休药期应为26d和32d。 中国对虾肌注恩诺沙星后，血液中药物浓度即刻达到峰值，并迅速向组织中分布，血药经时过程符合一级吸收二室开放模型，主要药动学参数为：T_1/2α0.094h、T_1/2β7.03h、AUC39mg／L.h、K₁₂3.59h^-1、K₂₁3.69h^-1，CLB0.25L／kg.h，药物在血液中的药-时复方新诺明和恩诺沙星在两种水产动物体内药物代谢动力学及残留研究曲线方程为c血液=3.93扩·38t+3.83e一01‘。药物在肌肉、肝胰脏内的经时过程亦符合一级吸收二室开放模型，主要药代参数分别为AUC73和320m叭.h、T，。KA 0.03和0 .06h、T，二刀19.7和597h，参数显示药物在这两种组织中分布广泛，药物向组织中运转的速度较快，消除速度较慢。药物在组织中的药一时曲线方程分别为C肌l、=4 .379e一04‘+2.57e一003‘一6.949e一22’3‘、e。，。，=8.99e一0·142‘+3.44e一o，’3，·6.949e一l”5‘。恩诺沙星的代谢物环丙沙星在三种组织中均能测到，其在肌肉，血液，肝胰脏中的主要参数分别为:Cn、a、0.009、0.023、0.183林咖U，AUC 0.139、0.466、7.2 mg/L.h，T，。K^0.17、0.x4、2.34h，TI/2K一0.3、13.3、Zo.7h，从数据可以看出环丙沙星在各组织中生成比较迅速，消除较慢，在肝胰脏中浓度最大。根据本试验结果，按照多计量给药原理，则中国又创吓肌注恩诺沙星合适的给药方案应为:6 .4mg瓜g的剂量，每日一次给药。更多还原

【Abstract】 This article could be divided into two parts, one part first reports the residual characteristics of SMZ and TMP in perch at different temperature following oral administration for 5 consecutive days. The concentrations of medicament were determined by High Performance Liquid Chromatography. The results indicated that The velocity of elimination and absorptivity changed at different temperature. They will increase when the temperature increase. The withholding period for perch after oraladministration at dose of 40mg kg-1 with mixture of SMZ and TMP (5/l)for 5 consecutive days should be 26d and 30d at water temperature 22℃ and 16℃.The other part part first reports pharmacoknetics of enroflxacin and its activated metabolite ciprofloxacin in Penaeus chinensis. after intramuscular injection. The concentration of medicament were determined by High Performance Liquid Chromatography. The data were analyed with the pharmacoknetics computer program MCPKP. The pharmacyoknetic showed that the concentration-time course of enroflxacin in plasma after intramuscular injection can be described by a two-compartment open model. The main pharmacoknetics parameters were as follows: T,/2 a 0.094h, T1/2B 7.03h, AUC 39 Mg/L.h, K12 3.59 h-1 , K21 3.69h-1. The theoretical equation was C血液 =3.93e-738t+3.83 e-0.1t. the concentration-time course of enrofioxacin in muscle and liver can be described by a two-compartment open model too. The main pharmacoknetics parameters were as follows: AUC 73 and 320 Mg/L.h > T1KA 0.03and 0.06h, T1/2 B 19.7 and 59.7h. The theoretical equation was C 肌肉 =4.379e-0.4t+2.57e-0.03tt-6.949e--22.73t, C 肝胰脏=8.99e-0.142t+3.44e-0.013t-6.949e-11.95t, Ciprofloxacin, The metab -olite of enrofioxacin can be detected in all three tissue. The values of main pharmacoknetics parameters Cmax(ug/ml),AUC(mg/L.h),T1/2KA(h)and T1/2K(h) were as follows: 0.009,1.26,0.17 and 10.3 for muscle, respectively, 0.023,0.95,0. 14and 13.3 for blood, respectively, 0.183,18.7,2.34 and 20.7 for liver, respectively. Base on the data above, we suggest dosage regimen of enrofioxacin is that Penaeus chinensis can take enrofioxacin once one day by intramuscular injection (6.4 mg/kg)更多还原