氟苯尼考及氟苯尼考胺在西伯利亚鲟体内的药动学及组织分布

Pharmacokinetics and tissue distribution of florfenicol and florfenicol amine in Acipenser baeri

采用液质联用法(HPLC-MS/MS)建立了氟苯尼考和氟苯尼考胺同时检测的方法,研究了氟苯尼考口灌给药西伯利亚鲟后,氟苯尼考及其代谢物氟苯尼考胺在西伯利亚鲟体内的药动学和组织分布。水温22℃下,氟苯尼考以15 mg/kg剂量单次口灌给药西伯利亚鲟,检测血浆、肝脏、肾脏和肌肉等组织中氟苯尼考及其代谢产物氟苯尼考胺的浓度,结果显示:氟苯尼考及其代谢产物氟苯尼考胺在西伯利亚鲟体内的药时数据均符合一级吸收二室开放模型,氟苯尼考在血浆中的达峰浓度(Cmax)为3.4μg/mL,达峰时间(Tpeak)为2.943 h,表观分布容积(V/F)为3.267 L/kg,消除半衰期(t1/2β)为31.21 h,药时曲线下总面积(AUC)为76.51μg.h/mL,Cmax(FFA)/Cmax(FF)和AUCFFA/AUCFF仅为5.44%和20.73%;氟苯尼考在各组织中分布广泛,分布规律相近,肝脏、肾脏中药物浓度较高。结果表明:氟苯尼考在西伯利亚鲟体内具有吸收迅速、达峰浓度高、消除相对缓慢及组织中分布广泛的特征且氟苯尼考主要以原形药物形式代谢消除。研究亮点:针对氟苯尼考目前广泛用于水产养殖中细菌性疾病防治的现状,本文首次采用液质联用法进行了氟苯尼考及其代谢产物氟苯尼考胺在西伯利亚鲟体内分布及代谢规律的研究。建立了比较简单的样品处理方法,并从药物本身和代谢产物整体来研究药动学及组织分布特征,为制定该药安全使用方法提供了理论基础。

Using high performance liquid chromatography with tandem mass spectrometric （HPLC-MS/MS） , we established a new method for detecting florfenicol and florfenicol amine which enabled us to study florfenicol, related metabolites （florfenicol amine） pharmacokinetics and tissue distribution of Acipenser baeri after oral administration of florvenicol in vivo. In this study, oral administration of florfenicol was performed on the Acipenser baeri at a dosage of 15 mg/kg body weight at 22 ~C, and the blood plasma, liver, kidney and muscle were then sampled to measure the concentration of florfenicol and its metabolite （florfenicol amine） using HPLC-MS/MS method. The results indicated that the concentration time course of florfenicol and florfenicol amine can be described by a two-compartment open model with first order absorption in vivo. The maximal concentration （Cmax） of florfenicol in blood plasma was 3. 4 μg/mL. Time-point of maximal concentration（Tpeak） was 2. 943 h. Volume of distribution （V/F） was 3. 267 L/kg. Half-life of elimination （t1/2β）was 31.21 h. Area under the timeoncentration curve （AUC） was 76.51 μg . h/mL, Cmax（FFA）/ Cmax（FF） and AUCFFA/UCFF were 5. 44% , 20. 73% ; Florfenicol and florfenicol amine were found to be extensively distributed and had a similar regularity in several tissues, with a higher concentration in liver and kidney. The results indicate that florfenicol have following features in Acipenser baeri： rapidly absorbed, high peak concentration, slow elimination and wide range of tissue distribution, and mainly metabolized or eliminated in the form of initial drugs.