本文采用体内药动学和体外药效学相结合的方法,应用Excel2007、药动学3p97软件和kinetica4.4软件进行数据处理和分析,研究了鲤鱼血清中甲砜霉素抗嗜水气单胞菌Aeromonashydropila的活性,为甲砜霉素在水产动物疾病预防和治疗细菌陛败血症提供理论依据。研究结果表明:给鲤单剂量口灌30mg·kg-1剂量的甲砜霉素后,药物在鲤体内吸收迅速,达峰快,消除缓慢。1.361h血药达峰(Tpeak),峰浓度(Cmax)为39.825μg·mL-1,吸收速率(Ka)为2.58h,分布半衰期T1/2(ka)为7.317h,滞后时间(TL)为0.234h,消除半衰期T1/2(ke)为77.292h。在半效应室内,EC50为15.62h。PK-PD同步模型参数AUC/MIC血清为35.37h,Cmax/MIC血清为24.89。通过抑制效应SigmoidEmax模型得到8.52~47.94mg·kg-1为临床使用甲砜霉素(TAP)防治鲤鱼细菌性败血症的给药剂量。建议甲砜霉素在预防和治疗细菌性败血症的最佳给药方案为:药饵的治疗剂量为47.94mg·kg-1,预防剂量为8.52mg·kg-1。
The anti-bacterium A eromonas hydropila activity of thiamphenicol was studied in serum of songpu mirro carp (Cyprinus carp L. ) fed thiamphenicol (TAP) by oral administration by pharmacokinetics and in vitro pharmacodynamics model via Excel 2007, 3p97 and kinetica 4.4 to provide important theoretical basis for application of TAP in disease treatment. The TAP was shown to be ab- sorbed quickly, eliminated slowly and to have a peak rapidly in Songpu mirror carp single oral administration at a dose of 30 mg kg-1 body weight. It was found to be 1.361 h for Try, 39.825μg·mL-1 for Cmax 2.58 h for Ka, 7.317 h for T1/2 (ka), 0.234 h for TL and 77.292 h for T1/2 (ke), and. 15.62 h for ECs0was. PK-PD parameters were 35.37 in AUC/MIC and 24.89 in Cmax/MIC. Sigmoid Emax model revealed that the TAP drug was administrated at a dose of 8.52-47.94 mg·kg-1. It is suggested that the optimal dose be 47.94 mg·kg-1 body weight for therapy and 8.52 mg·kg-1 body weight for prophylaxis of bacterial sepsis when the TAP is added into diet.