诺氟沙星盐酸小檗碱预混剂在眼斑拟石首鱼体内的药代动力学和残留消除规律研究

Pharmacokinetics and the residues elimination regularity of Norfloxacin and Berberine hydrochloride premixin Sciaenops ocellatus

关键词:  诺氟沙星盐酸小檗碱预混剂  眼斑拟石首鱼  药代动力学  残留消除

Key words:  Norfloxacin and Berberine hydrochloride premix  Sciaenops ocellatus  pharmacokinetics  Elimination of residues

摘要:

研究诺氟沙星盐酸小檗碱在眼斑拟石首鱼体内的药代动力学和残留消除规律。在水温28±2℃、盐度28条件下,诺氟沙星(Norfloxacin,NFLX)盐酸小檗碱(Berberine hydrochloride,BBH)预混剂按450 mg/kg的剂量口灌眼斑拟石首鱼后, 其血浆、肌肉、肝脏、和肾脏中的药物浓度用HPLC-MS/MS测定,药时数据用DAS3.0软件分析。结果显示：单剂量口灌给药后,眼斑拟石首鱼血浆中NFLX和BBH的药时数据均符合一级吸收二室模型；血药达峰时间(tp)分别为1.20和1.79 h,血药浓度峰值(Cmax)分别为358.40和144.89 μg/L,药时曲线下面积(AUC0-∞)分别8252.80和6454.52 μg/(L.h),消除半衰期(t1/2β)分别为43.26和27.30 h；NFLX和BBH在鱼体各组织中的分布较广,灌服给药后,肌肉、肝脏和肾脏中NFLX和BBH的Cmax分别为418.05和230.76 μg/kg、1745.94和901.09 μg/kg、1143.45和997.09 μg/kg,tp分别为1.5和1.5 h、1.5和2.0 h、1.5和2.0 h,AUC0-∞分别7682.00和5596.30 μg/(kg.h)、31236.90和19096.85 μg/(kg.h)、22593.93和37509.17 μg/(kg.h)；NFLX和BBH在眼斑拟石首鱼体内消除速度较慢,灌服给药后肌肉、肝脏和肾脏的t1/2β分别为33.41和61.81 h、20.44和15.04 h、30.28和23.43 h。按450 mg/kg剂量连续5 d口灌给药后,眼斑拟石首鱼血浆、肌肉、肝脏、肾脏中的NFLX和BBH残留消除半衰期(t1/2)分别为：30.24和33.33 h、40.76和61.60 h、38.68和36.96 h、43.77和59.40 h。以10 μg/kg为最高残留限量,肌肉作为食用靶组织,在本试验条件下,建议休药期不得少于12 d。

Abstract:

To investigate the pharmacokinetics and elimination regularity of residues in plasma and tissue of Sciaenops ocellatus with a single dose of 450 mg/kg body weight after oral administration at the water temperature of 28±2 ℃ and salinity of 28 by HPLC-MS/MS method. Pharmacokinetics parameters were calculated by DAS3.0 software．Results showed that Norfloxacin (NFLX) and Berberine hydrochloride (BBH) premix concentration-time date in plasma of S. ocellatus were described as a two-compartment model with first-order absorption. The peak time (tp), the maximum concentration (Cmax), the area under the concentration-time curve (AUC 0-∞) and the elimination hal-life (tl／2β) of NFLX and BBH in plasma were 1.20 and 1.79 h, 358.40 and 144.89 μg/L, 8252.80 and 6454.52 μg/(L.h), 43.26 and 27.30 h, respectively. The present results indicated that NFLX and BBH in S. ocellatus after oral administration had the ability to distribute widely to diverse tissues and eliminated slowly. The Cmax of NFLX and BBH in muscle, liver and kidney were 418.05 and 230.76 μg/kg, 1745.94 and 901.09 μg/kg, 1143.45 and 997.09 μg/kg, tp were 1.5 and 1.5h, 1.5 and 2.0 h, 1.5 and 2.0 h, AUC0-∞ were 7682.00 and 5596.30 μg/(kg.h), 31236.90 and 19096.85 μg/(kg.h), 22593.93 and 37509.17 μg/(kg.h), t1/2β were 33.41 and 61.81 h, 20.44 and 15.04 h, 30.28 and 23.43 h, respectively. S. ocellatus after oral administration continuous with 450 mg/kg dose for 5 days, The t1/2 of NFLX and BBH in plasma, muscle, liver and kidney were 30.24 and 33.33 h, 40.76 and 61.60 h, 38.68 and 36.96 h, 43.77 and 59.40 h, respectively. If the maximum residue limits (MRL) for 0.01 mg/kg and the muscles as edible target tissue, the withdrawl period should be no less than 12 days under this experiment condition.