【作者】 李艳华；

【导师】 佟恒敏；

【作者基本信息】 东北农业大学 ， 兽医药理学， 2000， 硕士

【摘要】 盐酸沙拉沙星是一种动物专用的氟喹诺酮类药物。本文以高效液相色谱法（HPLC）为定量手段，研究了盐酸沙拉沙星在成年健康蛋鸡血液和组织中的经时过程以及盐酸沙拉沙星在组织中的残留。并运用回归分析的方法，研究血液和组织间含药量的动态相关关系，建立组织含药量的间接预测方程。由单剂量给药参数，算出多剂量给药参数，为临床应用提供理论依据。 采用MCP-KP自动化药动学分析程序对数据进行分析。药动学结果表明：蛋鸡单剂量口服盐酸沙拉沙星后（10mg/kg），血液经时过程符合一级吸收一室开放式模型，其理论方程为：C_b=1.036(e^-0.1735t-e^-2.057t)，主要动力学参数t_1/2k3.793hrs、t_max1.5807hrs、c_max0.7429μg/ml、AUC5.3790μg/ml.h。 组织中的盐酸沙拉沙星的经时过程：心脏符合一级吸收三项指数方程，理论方程为：C_h=0.1455e^-0.0243t+2.484e^-0.54403t-2.629e^-0.8617t，主要动力学参数t_1/2B7.765hrs、t_1/2a1.6027hrs、t_max1.6826hrs、c_max0.5129μg/ml、AUC9.0265μg/ml.h。 肾脏符合一级吸收三项指数方程，理论方程为：C_k=1.703e^-0.126t+0.3283e^-0.2111t-2.0312e^-0.4976t，主要动力学参数t_1/2B40.26hrs，t_1/2a4.418hrs、t_max1.9855hrs、c_max0.9090μg/ml、AUC10.894μg/ml.h。 肝脏符合一级吸收二项指数方程，理论方程为：C_l=6.732(e^-0.18103t-e^-0.1108t)，主要动力学参数t_1/2k3.1587hrs、t_max1.9764hrs、c_max3.737μg/ml、AUC31.354μg/ml.h。 肌肉符合一级吸收二项指数方程，理论方程为：C_m=0.9188(e^0.1579t-e^-0.2014t)，主要动力学参数t_1/2k4.124hrs、t_max3.5679hrs、c_max0.6956μg/ml、AUC5.3269μg/ml.h。 组织动力学研究结果表明：盐酸沙拉沙星的组织含药量，以肝脏最高，肾脏、肌肉次之，心脏最低，但均超过多数敏感菌株的最低抑菌浓度。根据血清和组织中药物消除规律推算出药物浓度降至0.01μg/ml所需时间，血液、心脏、肝脏、肾脏、肌肉分别为25.58、49.83、32.63、160.02、29.43（hrs），以肾脏中药物残留时间长。 对血药浓度与组织药物浓度进行一元线性回归、多元线性回归和一元曲线回归分析。结果表明，这三种分析方法均能较好地研究血药浓度与组织药物浓度的动态变化规律，且曲线回归在分析的整体性及准确性方面优于直线回归。利用各种回归方程，可达到间接预测组织含药量的目的。更多还原

【Abstract】 Sarafloxacin Hydrochloride is one of floroquinolones only used for animals infectious diseases.In this thesis, the pharmacokinetics process of sarafloxacin Hydrochloride of chicken and the residue in tissue of chicken are studied by using the (High performance liquid chromatography,HPLC) procedure. The dynamic interrelated relationship of the drug level between serum and tissue were analyzed by the use of the regression analysis, and the indirectly predictive equation about the drag concentration in tissue is established. The data were analyzed with the Pharma~olinetics computer program MCP-KP. Phamiacolinetics show that the blood concentration-time course can be described with the first compartment open model with the first order absorption alter oral administration( 10mg/kg) .Its theoretical equation was as follows: CbI .036 (eI735t - e2057t), its main pharmacokinetics parameters t1,.3.793his. t...I.5807brs.. c0.7429 i g/ml.. AUC5.3790 i g/ml. h0 The kinetics process Sarafloxacin Hydrochloride in tissues: the heart concentration -time (C1-T) data of Sarafloxacin Hydrochloride was best described by a triexponential equation with flint order absorption.Its theoretical equation was as follows: Ch = 0.1455e0 43+2.484& OS44O3L2629e lS6I7t its main pharmacokinetics parameters t117.765hrs t111 .6027 tl.6826 hrs c0.5129 j.i g/ml . AUC9.0265 .t g/ml. h0 The heart concentration -time (C-T3 data of Sarafloxacin Hydrochloride was best described by a triexponential equation with first order absorption.Its theoretical equation was as -O.12&-02111t -04976t follows: Ck = I .703e +0.3283e -2.031 2e , its main pharmacokinetics parameters t1, 40.26 hrs.. t4.418hrs. t 1.9855 hrs c0.9090 i g/ml., AUC1O.894 .t g/ml. h The liver concentration -time (C1-T3 data of Sarafloxacin Hydrochloride was best described by a biexponential equation with first order absorption.Its theoretical equation was as -018103t .O1IO& follows: C1= 6.732(e - e ), its main pharmacokinetics parameters tl,2k3.1587hIS t1,1.9764hrs. c3.737 j.t gin 1.. AUC31.354 5.1 giml. h. The muscle concentration -time (C1-T1) data of Sarafloxacin Hydrochloride was best described by a biexponential equation with first order absorption.Its theoretical equation was as follows: Cm 0.91 88(e0157 - eO2OI4t) its main pharmacokinetics parameters t112k4. l24hrs-. t,3.5679hrs.. c0.6956 ji giml.. AUC5.3269 g/ml. hrs. Tissue phannacokinetics indicates Sarafloxacin Hydrochloride concentration in tissue is the highest for liver, and lower for kidney and muscle, and the lowest for the heart. And the residue time of drug in kidney is longer than that in the other tissue..According to the elimination regularity of serum. heart liver., kidney and muscle,the time taken by the drag concentration dropping to 0.OIug/ml is calculated.They were 5.58(hrs), 49.83(hrs), 32.63brs) ,160.02(hrs), 29.43(hrs). The drug concentration in serum and tissue is analyzed by the use of the liner regression equation in one unknow and multi-unkow, and the curvilinear regression equation in one unkow. The results indicate that the dynamic variation regularity of the drug concentration in serum and tissue can be better studied with this two analysis method, and the curvilinear regression is better than the linear one in entirety and accuracy.The purpose of prediction the drug concentration in tissue indirectly is achieved by the use of various regression equations.更多还原