噁喹酸和氟甲喹在鳗鱼体内的药代动力学研究

Pharmacokinetic study of oxolinic acid and flumequine in Muraenesox cinereus

研究了单次血管注射喹酸(Oxolinicacid)和氟甲喹(Flumequine)后,在鳗鱼(Muraenesoxcinereus)体内的代谢规律及残留情况。采用高效液相色谱-质谱联用(HPLC-MS)法进行喹酸和氟甲喹的检测,检测低限(LOD)1ng/ml;定量限(LOQ)5ng/ml。喹酸和氟甲喹的代谢过程均可以用一级代谢二室模型来描述,喹酸的分布半衰期:0·18h,消除半衰期:14·84h,总体清除率0·07L/kg·h;氟甲喹的分布半衰期:0·19h,消除半衰期:9·38h,总体清除率0·07L/kg·h。两种药物在鳗鱼体内都有很强的“首过效应”,易在胆汁中积累;给药72h后,喹酸和氟甲喹在可食用组织肌肉中的残留量分别为36·1ng/g和21·8ng/g,低于目前国外要求的最高残留量50ng/g和75ng/g。

Studies were conducted on the pharmacokinetics properties and residue depletion of oxolinic acid and flumequine in Muraenesax cinereus held in seawater at 22.5 ＋ 1℃ after vascular administration. Residues of oxolinic acid and flumequine were detected with HPLCMS. Limits of detection（LOD） and limits of quantitation（LOQ） of this method were lng/ml and 5ng/ml, respectively. The metabolic process of both oxolinic acid and flumequine could be described by a two-compartment model of first-degree metabolism. The calculated distribution half life （t1/2 α）, elimination half life （t1/2 β）, and total body clearance （C1T） of oxolinic acid were 0.18 h, 14.8 h and 0.07 （L/kg） · h, respectively. The calculated distribution half life （t1/2 α）, elimination half life （t1/2 β）, and total body clearance （ClT）of flumquine were 0. 19 h, 9.38 h and 0.07 （L/kg） · h, respectively. Both the drugs had significance first-pass effect inMuraenenesox cinereus and easily accumulated in bile. The concentrations of oxolinic acid and flumequine in muscle 72h after vascular administration were 36.1 ng/g and 21.8ng/g, lower than the maximum residue limit （MRL） of 50ng/g and 75ng/g demanded by European Union.