磺胺二甲嘧啶及其乙酰化代谢产物与血浆蛋白体外结合特点  

IN VITRO BINDING PROPERTIES OF SULFAMETHAZINE AND ITS ACETYL METABOLITE TO PLASMA PROTEIN

作　　者：肖超[1] 陈风春[1,2] 刘忠文[1,2] 张亦红[1,2] 刘芳[1,2] 刘飞[1,2] 周焕英[1,2] 高志贤[1,2] 

机构地区：[1]华中农业大学食品科技学院,武汉430070 [2]军事医学科学院卫生学环境医学研究所,天津市环境与食品安全风险评估重点实验室

出　　处：《解放军预防医学杂志》2012年第4期243-246,共4页Journal of Preventive Medicine of Chinese People's Liberation Army

基　　金：国家自然科学基金(No.30972442);天津市自然科学基金(No.09JCYBJC08300)

摘　　要：目的研究磺胺二甲嘧啶(SMZ)及N4-乙酰基磺胺二甲嘧啶(AcSMZ)与血浆蛋白体外结合特点,为进一步研究SMZ的药物代谢规律提供参考依据。方法经平衡透析的血浆样品以水浴超声的方式萃取,结合HPLC分析测定SMZ及AcSMZ的体外血浆蛋白结合率。结果当平衡透析温度为4℃和37℃时,SMZ和AcSMZ与血浆蛋白的结合率分别下降约20%和10%,乙酰化代谢快型个体在平衡温度37℃时,3种不同质量浓度SMZ(50、100、250μg/ml),和AcSMZ(50、100、120μg/ml)的血浆蛋白结合率分别为69%、74%、73%和89%、93%、91%,未见有浓度依赖关系;当不同质量浓度SMZ和AcSMZ一起同时与血浆蛋白结合时,SMZ结合率较单独SMZ与血浆蛋白的结合率无明显差别,分别为68%、69%、65%和69%、74%、73%。乙酰化代谢慢型个体在平衡温度为4℃时,所得结果也相似。结论 SMZ和AcSMZ与血浆蛋白的结合不具有浓度依赖性;AcSMZ对SMZ与血浆蛋白的结合竞争性不明显;平衡透析温度会影响药物母体及代谢物与血浆蛋白的亲和力,从而影响其与蛋白的结合率;乙酰化代谢类型不影响以上结合特性。Objective To study the binding properties of sulfamethazine （SMZ） and N4-acetyl sulfamethazine （AcSMZ）to plasma protein, so as to provide reference data for further studying the metabolism of SMZ. Methods The plasma sample by equilibrium dialysis was extracted with ultrasonic bath, and the binding rate of SMZ, AcSMZ to plasma protein was assayed with HPLC. Results When the equilibrium temperature was 4 ℃, and 37 ℃, the binding rate of SMZ, AcSMZ to rabbit plasma protein decreased by about 20%, 10% respectively. The binding rate of different concentrations of SMZ （50, 100,250ug/ml）, and AcSMZ （50,100,120 ug/ml） to plasma protein were 69% ,74% ,73%; 89% ,93% ,91% respectively at 37 ℃and fast acetylation, indicating a non-concentration-dependent relationship. When different concentrations of SMZ together with AcSMZ bound to plasma protein, the binding rate of SMZ was not significantly different from that of SMZ alone （68 %, 69 %, 65 % ; 69 %, 74%, 73 % ）. The results obtained at 4 ℃ and slow acetylation were similar to those mentioned above. Conclusion The binding of SMZ and AcSMZ to plasma protein was non-concentration-dependent. The competition of AcSMZ with SMZ for binding to plasma protein was not obviously seen. Different equilibrium temperature may alter the affinity of target compounds and plasma protein, so as to affect the bind- ing rate. The above mentioned properties were not different between fast and slow acetylation.

关 键 词：磺胺二甲嘧啶 N4-乙酰基磺胺二甲嘧啶 HPLC-UV 血浆蛋白 结合 

分 类 号：R978.2[医药卫生—药品]