磺胺二甲嘧啶在黄河鲤体内的代谢动力学研究

Pharmacokinetics Study of Sulfamethazine in Cyprinus carpio

为探究磺胺二甲嘧啶在黄河鲤体内的药物代谢动力学特征,在(23±2)℃水温条件下,以20 mg/kg剂量给黄河鲤进行单次静脉注射和口灌磺胺二甲嘧啶,分别于给药后0.25、0.5、1、2、4、6、12、24、48、72 h采集血液和各组织,利用高效液相色谱测定血液和各组织中磺胺二甲嘧啶及其代谢物N^(4)-乙酰化磺胺二甲嘧啶质量浓度,采用DAS 2.0软件分析血液中磺胺二甲嘧啶代谢动力学参数。结果显示,黄河鲤静脉注射磺胺二甲嘧啶后,血液中的药物代谢过程符合零级吸收二室开放模型,表观分布容积为0.911L/kg,消除半衰期为19.964 h;口灌磺胺二甲嘧啶后,血液中的药物代谢过程符合一级吸收二室开放模型,表观分布容积为1.406 L/kg,吸收半衰期为0.02 h,消除半衰期为16.927 h,达峰时间为1 h,峰质量浓度为17.90 mg/L,生物利用度为93.30%。黄河鲤口灌磺胺二甲嘧啶后,磺胺二甲嘧啶在肌肉、肝脏、肾脏和脑各组织器官均有分布,N^(4)-乙酰化磺胺二甲嘧啶除了在脑中未检出,在其他组织中均有检出。以上结果表明,口灌磺胺二甲嘧啶在黄河鲤体内吸收较快,消除也较快,组织分布广,生物利用度较高。结合磺胺二甲嘧啶对主要致病菌的体外抑菌浓度,依据其在黄河鲤体内的药物代谢动力学特点,提出口服给药方案:按照138 mg/kg剂量,每日1次,连续给药5~7 d。

The purpose of the study was to investigate the pharmacokinetic characteristic ofsulfamethazine in healthy Cyprinus carpio at the water temperature of(23±2)℃.C.carpio was sampled at 0.25,0.5,1,2,4,6,12,24,48,72 h after single intravenous and oral administration at a dose of 20 mg/kg sulfamethazine,respectively.The concentrations of sulfamethazine and its metabolite N^(4)-acetylsulfamethazine in the muscle,blood,kidney and liver were determined by high performanceliquid chromatography(HPLC).The pharmacokinetics data of sulfamethazine in the blood were analyzedusing the DAS 2.0 version pharmacokinetic software.The results showed that the plasmaconcentration-time data for sulfamethazine could be described by a two-compartment open model with thestepless absorption after intravenous administration,the apparent distribution volume(Vd)was 0.911 L/kg,the elimination half-time(T1/2β)was 19.964 h.The plasma concentration-time data forsulfamethazine could be described by a two-compartment open model with first-order absorption after oraladministration,the Vd was 1.406 L/kg,the absorption half-time(T1/2Ka)was 0.02 h,the T1/2βwas 16.927 h,time to peak concentration(Tmax)was 1 h,peak concentration(Cmax)was 17.90 mg/L and bioavailability(F)was 93.30%.After oral administration,sulfamethazine was distributed in muscle,liver,kidney andbrain,N^(4)-acetylsulfamethazine was detected in all tissues except for brain.The results indicated that thesulfamethazine was absorbed and eliminated quickly,distributed widely in all tissues and had highbioavailability in C.carpio after oral administration.According to the sulfamethazine pharmacokineticsand its antibacterial effect on most fish bacterial pathogens,the recommended dosage of sulfamethazinewas 138 mg/kg once per day by oral administration,continuously for 5-7 days.