噁喹酸、环丙沙星和磺胺二甲嘧啶在大菱鲆体内的药代动力学及其代谢酶基因CYP3A的克隆与表达分析-临床兽医学专业论文.docxVIP

上海海 上海海洋大学硕士学位论文 I III Pharmacokinetics of Oxolinic Acid, Ciprofloxacin, Sulfamethazine in Turbot and Molecular cloning and Expression analysis of its Cytochrome P450 3A Gene ABSTRACT Oxolinic acid, ciprofloxacin and sulfadimidine are commonly used in aquaculture of antibiotic. Cytochrome P450 is involved in drug metabolism in biology as the main enzymes, among which CYP 3A can metabolize most types of drugs, including antibacterial drugs and antiviral drugs. The reasonable dosage regimen of the three drugs were established by studying their pharmacokinetics. In order to provide theoretical basis for clinical drug rationally, the relations of drug metabolism, CYP3A expression and enzymes activity were also explored in this paper. The research was divided into three parts: The pharmacokinetics of Oxolinic acid was studied in Scophthalmus maximus by using the high performance liquid chromatography (HPLC). The study was performed at(24.5±0.2)℃. All the health fish received a single oral administration of OA at a level of 20mg/kg and intravenous administration of OA at a level of 10mg/kg. The results showed that the hemolymph concentration–time course of OA can be described by a two-compartment open model with the first order absorption after a single oral administration, the pharmacokinetic equation was: Cpo=2.059e-0.062t ＋ 0.645e-0.023t-2.704e-0.202t, the hemolymph concentration–time course of OA can be described by a two-compartment open model with the zero order absorption after a single intravenous administration, the pharmacokinetic equation was: Civ=12.284e-0.144t ＋0.284e-0.027t. The main pharmacokinetics parameters in plasma were those: The peak time,distribution and elimination half-lives (tmax,t1/2 α and t1/2 β ) by intravenous administration were found to be 0.083h,4.813h and 25.441h which were shorter than 6h,11.26h and 30.212h of oral administration. The results indicated that the peak time, absorption and elimi