【作者】 唐雪莲；

【导师】 佟恒敏；

【作者基本信息】 东北农业大学 ， 基础兽医学， 2002， 硕士

【摘要】 氯霉素是水产养殖中广泛应用的一类抗菌药物。本研究采用高效液相色谱法为定性、定量手段，研究了氯霉素在健康鲈鱼体内的药代动力学及在组织中的残留消除规律。由单剂量给药参数推算出多剂量给药方案，为临床用药提供理论依据；根据单剂量和多剂量给药后，药物在组织中的消除规律制定合理的休药期，为临床及公共卫生检测提供理论依据。 采用MCP-KP自动化药动学分析程序对数据进行分析。分析结果表明：鲈鱼单剂量口服氯霉素后（80mg/kg），血药经时过程符合一级吸收一室模型，其理论方程为：C_血液=30.815(e^-0.0614t-e^-0.662t)；主要动力学参数如下：K_a为0.662h^-1，T_1/2Ka，为1.047h；C_max为21.093μg/ml、T_max为3.961h、AUC为438.31mg.l^-1.h^-1；Kel为0.0614h^-1、T_1/2k为11.293h。 组织中氯霉素的经时过程均符合一级吸收二项指数方程，理论方程及主要动力学参数如下：C_肌肉=33.515(e^-0.085t-e^-0.219t，C_max为30.815μg/ml、T_max为7.079h、AUC为662.370mg.l^-1.h^-1、Kel为0.085h^-1、T_1/2K为8.174h。 C_肝脏=18.597(e^-0.062t-e^-1.854t)，C_max为14.231μg/ml、T_max为1.894h、AUC为226.910mg.l^-1.h^-1；Kel为0.062h^-1、T_1/2K为11.118h。 C_肾脏=26.024(e^-0.052t-e^-0.399t)，C_max为36.037μg/ml、T_max为5.889h、AUC为946.07mg.l^-1.h^-1；Kel为0.052h^-1、T_1/2K为13.424h。 多剂量（40mg/kg）给药后药物在组织中的消除可以用以下方程描述：C_血液=3.40e^-0.403t、C_肌肉=4.342e^-0.458t、C_肝脏=2.152e^-0.239t、C_肾脏=64.155e^-1.443t。按照消除方程，计算氯霉素在组织中达到0.01μg/ml所需要的时间，血液、肌肉、肝脏、肾脏分别为：14.164、13.261、22.476、6.075d。 药动学与组织动力学结果表明：氯霉素口服给药后，在鲈鱼体内吸收迅速，分布广泛，体内消除半衰期较长。组织中药物浓度较高，高于氯霉素对大多数细菌的最小抑菌浓度（0.01～5μg/ml）。根据血液与组织动力学参数，结合临床应用，提出合理给药方案为：按照40mg/kg.b.w的剂量，每日一次。 根据单剂量和多剂量给药后药物在组织中的消除规律，制定合理的休药期为大于23天。更多还原

【Abstract】 Chloramphenico1 is one of the antibiotics widely used in aquacuIture. In this study, thepharmacokinetic and residuaI characteristics of Chloraznphnicol in hea1thy Perch are studiedby using the High Performance Liquid Chromatography. In order to provide the theoreticalbases fOr the clinical use of Chloramphnicol, the multiple-dose pharmacokinetic parameterswere assessed according to the single-dose pharmacokinetic parameters. The withdrawal timewas deduced by the elimination of ChloramphnicoI, which must be usefu1 to the residuemonitoring fOr public heaIth.Data were analyzed with the pharrnacokinetic coniputer program MCP-KP. The resultsshowed that the plasma concentration-time course of ChloramphnicoI can be described by aone-compartment open model with the first order absorPtion after oraI administration(80mg/kg). Its theoretical equation was as foIlows: C bItal = 30.8l5 (e -- o.oo14 t - e -- o.bo2 l ), andthe main pharmacokinetic parameters were those: K. 0’662h-l, T l/2K. I ’047h, C max 2l ’093 llg/mI, T max 3 ’96l h, AUC 438.3 l mg.l-’.h-’, Kel 0.06l4h-’, T,l2k l l .293h.The kinetics process of Chloramphnicol in tissues can all be described by thebiexponential equation with the first order absorption, and the theoreticaI equations and themain pharmacokinetic parameters were as follows fC muscIe = 33’515 (e -- o.os5 t - e - 9’2l9 t ), C max 30’8l5 P g/ml, T m.x 7’079h, AUC662.370mg. l-I .h-’,KeI 0.085h-I, T,,,k 8. 1 74h.C li..,= l 8’597 (e -- o.o62 t - e -- l’854t ), C max I 4.23 l u g/ml, T mtx l ’894h, AUC 226.9l0mg.I-’.h", Kel0.062h- ’, T,,2k I l. l l8h.C kidney = 26’024 (e -- o.o52 l- e -- o.399 l ), C mas 36.037 u g/ml, T m.x 5’889h, AUC 946.07mg.l’’.h-’, Kel 0.052h", T,,,k l3.424h.The elimination characteristics of muItipIe-dose administrition (40mg/kg) can bedescribed by the equations aS fOllows f C bl- = 3.40 e -- o.4o3 1’ C mutcIe = 4’342 e -o.45a l’ C liv,l= 2.l52 e -o.239 t’ C kideey = 64.l55 e - I’M3 t. According to the equations, the time taken by theconcentrations of Chloramphnicol dropping to 0.0l ll glml in blood. muscle. Iiver and kidneywas l4.l64. l3.26l’ 22.476. 6.075 days respectively.The resuItS of phdriacokinetic and residual studies show that after oraI administration,Chloramphnicol can be absorbed quickly. distributed widely and eliminated slowly. The2concentrations in tissues were so high that they are almost higher than the MIC ofChloramphnicoI fOr most bacteriec Acc6rding to the pharmacokinetic parameters, bindingwith the use in the clinic, we suggest the reasonab1e administration project as that the Perchcan be given Chloramphenicol once a day by the oral administration dose of 40mg/kg bodyweight.According to the regular of ChIoraznphenicol elimination, we suggest the withdrawaltime should be about twenty-three days.更多还原