单次和连续药饵投喂方式下复方磺胺嘧啶在吉富罗非鱼体内的代谢消除规律  

Pharmacokinetic and residues of compound sulfadiazine in GIFT(Oreochromis niloticus) at single and multiple dosage

作　　者：王伟利[1] 肖贺[1,2] 姜兰[1] 罗理[1] 张瑞泉[1] 谭爱萍[1] 邓玉婷[1] 

机构地区：[1]中国水产科学研究院珠江水产研究所,农业部渔用药物创制重点实验室,广东省水产动物免疫技术重点实验室,广东广州510380 [2]上海海洋大学水产与生命学院,上海201306

出　　处：《中国渔业质量与标准》2016年第1期29-35,共7页Chinese Fishery Quality and Standards

基　　金：公益性行业(农业)科研专项(201203085);广东省鱼病防治专项资金(2012年)

摘　　要：在120mg／kg单次药饵投喂和首剂量投喂复方磺胺嘧啶（磺胺嘧啶：甲氧苄啶=5：1）120mg／kg后，再按60mg／kg的剂量连续5d投喂条件下，采用HPLC法研究了复方磺胺嘧啶在吉富罗非鱼（Oreochromis niloticus）体内的代谢消除规律。结果显示，单次给药下磺胺嘧啶和甲氧苄啶在罗非鱼血浆、肌肉、肾脏和肝脏中的消除半衰期（t1/2ke）分别为16．82和5．99，23．40和13．49，13．43和6．53，15．9和11．02h，甲氧苄啶在各组织中的消除均快于磺胺嘧啶。给药24h内，药物在各组织中的比值（SD：TMP）均在1—40：1（除了肾脏4h采样点为0．71）的理想抑菌浓度范围内，提示5：1给药比例在罗非鱼上使用能够达到理想的体内抑菌效果。血浆较组织中具有更高的比值，这与甲氧苄啶在体内的快速分布特性一致。连续给药情况下，磺胺嘧啶的浓度较单次给药情况下显著提高，甲氧苄啶的浓度较单次给药并未显著提高，这可能与甲氧苄啶较快的代谢速率及体内快速分布有关。参考中华人民共和国农业部NY5070-2002号公告中对水产品中磺胺类药物总量最大残留限量（MRL）为0．1mg／kg，甲氧苄啶MRL为0．05mg／kg的规定，单次给药和连续给药情况下，计算的休药期结果一致，建议本实验条件下的休药期不低于12d。HPLC method was used to study the pharmacokinetics and tissue residual of compound sulfadiazine （ sulfa- diazine： trimethoprim =5：1 ） in GIFT after a single dose of 120 mg/kg body weight or an initial dose of 120 mg/kg body weight following a 5 d consecutive dose of 60 mg/kg body weight. Result showed： The elimination half - life （tl/2 ks） in plasma, muscle, kidney and liver were 16.82 and 5.99, 23.40 and 13.49, 13.43 and 6.53, 15.9 and 11.02 h for sulfadiazine and trimethoprim at single - dose, respectively. Trimethoprim was more quickly eliminated than sulfadiazine in all the tissues. The ratio of SD： TMP were between the optimal ratio of 1 -40：1 within 24 h in each group （ expect 0.71 at 4 h in kidney）, which indicated the rationality dosage of compound sulfadiazine in GIFT. The ratio was higher in plasma than in tissues, which was consistent with the rapid distribution characteristics of TMP. The concentration of sulfadiazine in multiple dosage had improved significantly than that in single - dose, while the concentration did not increase significantly for TMP. This may be related to the faster metabolism and rapid distribu- tion of TMP. According to the MRL of 0.1 mg/kg for sulfonamides and 0.05 mg/kg for trimethoprim in fishes in the NY 5070-2002 Announcement issued by the Ministry of Agriculture of the People＇ s Republic of China, the with- drawal time should not be less than 12 d under this experiment condition.

关 键 词：吉富罗非鱼 复方磺胺嘧啶 药物动力学 休药期 

分 类 号：S948[农业科学—水产养殖]