盐酸氯苯胍在斑点叉尾鮰体内的药代动力学及残留消除规律

在水温(28±1)℃条件下, 以20 mg/kg剂量的盐酸氯苯胍口灌斑点叉尾鮰(Ictalurus punctatus), 采用高效液相色谱-串联质谱法研究盐酸氯苯胍在斑点叉尾鮰体内的药代动力学和残留消除规律。结果显示, 在单次口灌给药后, 盐酸氯苯胍在斑点叉尾鮰血浆中的药时曲线符合二室模型特征, 其药动学方程为C= 7.69e–0.02t+ 0.13e–0.01t–7.82e–0.27t。盐酸氯苯胍在斑点叉尾鮰血浆、肌肉、皮、鳃、肝脏和肾脏中的T_(peak)分别为10.03、15.79、11.10、2.61、12.89、7.87h; C_max分别为5.76 μg/mL、2.91、2.90、3.05、3.04、0.42 mg/kg, 消除半衰期分别为58.63、23.57、35.37、19.74、29.34、43.30h; 药-时曲线下面积AUC分别为326.74 (μg/mL)/h、157.58、183.72、95.09、174.82、29.85 (mg/kg)/h。在连续口灌给药5d后, 停药后盐酸氯苯胍在斑点叉尾鮰肠道中的浓度最高, 肌肉中浓度最低, 盐酸氯苯胍在体内各组织中的消除速度由高到低依次为血浆、鳃、脑、肌肉、皮肤、肝脏、肾脏、肠。若将10 μg/kg作为盐酸氯苯胍的最高残留限量, 在试验条件下, 建议盐酸氯苯胍在斑点叉尾鮰体内的休药期至少应为23d。

PHARMACOKINETICS AND ELIMINATION REGULARITY OF ROBENIDINE HYDROCHLORIDE RESIDUES IN ICTALURUS PUNCTATUS

To assess tissues distribution and elimination of robenidine hydrochloride in Ictalurus punctatus, single and 5-day continuous oral administration (20 mg/kg) of robenidine hydrochloride has been conducted in healthy Ictalurus punctatus at (28±1)℃. The concentration-time curve of robenidine hydrochloride in plasma was a two-compartment model for the single oral administration with the kinetic equation: C= 7.69e–0.02t + 0.13e–0.01t–7.82e–0.27t. The T_(peak) and C_max in the plasma, muscle, skin, gill, liver and kidney of channel catfish were 10.03, 15.79, 11.10, 2.61, 12.89, 7.87 and 5.76 μg/mL, 2.91, 2.90, 3.05, 3.04 and 0.42 mg/kg, respectively. The elimination half-life and drug-time curve AUC were 58.63, 23.57, 35.37, 19.74, 29.34, 43.30h and 326.74 (μg/mL)/h, 157.58, 183.72, 95.09, 174.82, 29.85 (mg/kg)/h, respectively. For the 5-day continuous oral administration at 20 mg/kg, the highest and lowest concentration of robenidine hydrochloride was the intestines and the muscle, respectively. The elimination rate of robenidine hydrochloride in each tissue from fast to slow was plasma, gill, brain, muscle, skin, liver, kidney and intestines. If the maxi-mum residue limit (MRL) of robenidine hydrochloride in edible tissue is 10 μg/kg, the withdraw period should not be less than 23 days under this experimental condition.