肌注和口服药饵麻保沙星在日本对虾体内的药代动力学比较

摘要

The pharmacokinetics of intrasinusly, intramuscularly and orally administered marbofloxacin was deter-mined in kuruma prawn, Marsupenaeus japonicus, with a single dose of 10 and 30 mg/kg body weight respectively, at water temperatures of 25 ±0.6 . Following intramuscular and oral administration, the plasma concentr℃ ℃ a-tion-time data for enrofloxacin were best described as a two-compartment open model with first-order absorption and elimination with the pharmacokinetic equation: Cim =15.521e–1.153t+7.90e–0.059t-23.421e–11.73t and Cpo =17.486e–0.399t+3.01e–0.051t-20.496e–0.408t, respectively. After intramuscular and oral administration, the main pharmacokinetic parameters were as follows:t1/2Ka 0.059 and 1.697, tmax 0.25 h and 2.0 h, t1/2α0.601 h and 2.103 h, Cmax 20.785 mg/L and 12.4774 mg/L, F 99.56% and 69.68%, t1/2β 11.769 h and 13.535 h, respectively. It indicated quicker absorption, wider distribution, higher peak plasma concentration, higher bioavailability and faster elimina-tion by intramuscular administration than oral administration. In this study, pharmacokinetic parameters, post anti-biotic effect (PAE) and the minimum inhibitory concentration (MIC) were combined to discuss the dosage regimen of marbofloxacin. The scheme of marbofloxacin was established to shrimp bacterial disease, at the intervals of 13.6 and 11.8 h, with the dose of 14.30 and 19.17 mg/kg by intramuscular and oral administration, respectively.%　　在水温(25±0.6)℃条件下,分别以10、10和30 mg/kg剂量给健康日本对虾血窦注射、肌注和口服药饵麻保沙星后,用高效液相色谱法测定药物浓度,采用 DAS2.0药动学软件对血药浓度进行分析,主要比较了肌注和口服药饵两种给药方式下麻保沙星在日本对虾体内的药代动力学差异。结果显示,血窦注射给药后,麻保沙星在日本对虾体内药物动力学最佳模型为无级吸收二室开放模型,表达方程为： C 血窦注射=13.373e–1.396 t ＋8.28e–0.062 t；肌注和口服药饵麻保沙星后,在日本对虾体内的代谢过程均符合一级吸收二室开放模型,表达方程为 C 肌肉注射=15.521e–1.153t ＋7.90e–0.059t －23.421e–11.73t, C 口服药饵=17.486e–0.33t ＋3.01e–0.051t －20.496e–0.408t。与口服药饵给药后药代动力学参数比较,肌注给药后的tmax(0.25 h)、t1/2Ka(0.059 h)、t1/2α(0.601 h)和t1/2β(11.769 h)均小于口服药饵给药的tmax(0.5 h)、t1/2Ka(1.697 h)、t1/2α(2.103 h)和 t1/2β(13.535 h),且 Cmax(20.7858 mg/L)和 F(99.56%)均大于口服药饵给药 Cmax(12.4774 mg/L)、F(69.68%)。结果表明,肌注麻保沙星在日本对虾体内的吸收、分布和消除均快于口服药饵给药,且比口服给药吸收较完全。本实验将药动学参数与抗菌后效应(PAE)和最小抑菌浓度(MIC)相结合来探讨麻保沙星的给药方案,建议在治疗日本对虾细菌性疾病时,肌注14.30 mg/kg,每隔13.6 h一次；口服19.17 mg/kg,每隔11.8 h一次。