环丙沙星和磺胺二甲嘧啶在大菱鲆体内的药代动力学比较

Pharmacokinetics of Ciprofloxacin and Sulfamethazine in Turbot (Scophthalmus maximus) after a single Oral and Intravenous Administration

关键词:  大菱鲆  环丙沙星  磺胺二甲嘧啶  药代动力学  给药方案

Key words:  Scophthalmus maximus  Ciprofloxacin  Sulfamethazine  Pharmacokinetics  Dosage regimen

摘要:

采用高效液相色谱法,在(23.1?0.8)℃水温条件下,对环丙沙星和磺胺二甲嘧啶两种抗菌药物在健康大菱鲆体内的代谢动力学规律进行了比较研究。结果显示,单次口服环丙沙星和磺胺二甲嘧啶后,药物在血浆中的经时过程均符合一级吸收二室开放模型,表达方程分别为C_CIP=14.811e_-0.337t＋4.028e_-0.063t－18.839e_-0.616t、C_SM2=64.981e_-0.141t＋4.59e_-0.004t－69.571e_-0.19t；静脉注射这两种药物后,药物在血浆中经时过程均符合无级吸收二室开放模型,表达方程分别为C_CIP=21.784e_-1.098t＋1.514e_-0.043t、C_SM2=33.028e_-5.687t＋8.674e_-0.013t。口服相同剂量(20mg/kg)药物后,对血浆的药代动力学参数进行比较,环丙沙星的Tmax(6h)、Cmax(5.385μg/mL)、t_1/2Ka(1.125h)、t_1/2α(2.057h)和t_1/2β(11.028h)均小于磺胺二甲嘧啶给药(8h、13.990μg/mL、3.647h、4.923h和173.407h),且F(60.57%)大于磺胺二甲嘧啶给药F(47.13%)。证实环丙沙星在大菱鲆体内的吸收、分布、消除速度,达峰时间均快于磺胺二甲嘧啶给药,且比磺胺二甲嘧啶给药吸收完全。根据本实验的结果,环丙沙星和磺胺二甲嘧啶的合理给药方案分别为28.01mg/kg和18.32mg/kg,均为每日1次给药,连用3-5天。

Abstract:

The pharmacokinetics of ciprofloxacin and sulfamethazine was studied in Scophthalmus maximus by using the high performance liquid chromatography (HPLC). The study was performed at(23.1?0.8)℃. All the health frish received a single oral administration of CIP and SM2 at a level of 20mg/kg and intravenous administration of CIP and SM2 at a level of 10 mg/kg. The results showed that the hemolymph concentration–time course of CIP and SM2 can be described by a two-compartment open model with the first order absorption after a single oral administration, the pharmacokinetic equations were: CCIP=14.811e-0.337t＋4.028e-0.063t－18.839e-0.616t、CSM2=64.981e-0.141t＋4.59e-0.004t－69.571e-0.19t; the hemolymph concentration–time course of CIP and SM2 can be described by a two-compartment open model with the stepless absorption after a single intravenous administration, the pharmacokinetic equations were: CCIP=21.784e-1.098t＋1.514e-0.043t、CSM2=33.028e-5.687t＋8.674e-0.013t. After the same dose oral drugs, the main pharmacokinetics parameters in plasma were those: The peak time, peak concentration, absorption, distribution and elimination half-lives (Tmax，Cmax，t1/2Ka, t1/2α and t1/2β) by ciprofloxacin administration were found to be 6h, 5.385μg/mL, 1.125h, 2.057h and 11.028h which were shorter than 8h, 13.990μg/mL, 3.647h, 4.923h and 173.407h of sulfamethazine administration,but its bioavailability 60.57% were bigger than sulfamethazine administration which was 47.13%. The results indicate that the peak time, absorption, distribution and eliminate speed of Ciprofloxacin administration were faster than sulfamethazine administration, ciprofloxacin was absorbed completely. To the experimental results, the scheme of ciprofloxacin and sulfamethazine was established to fish bacterial diseases, with the dose of 28.01 mg/kg and 18.32 mg/kg at the interval of 1d, continuous 3-5days by oral administration,respectively.