注射用重组人肿瘤坏死因子α衍生物a的临床药代动力学.docVIP

注射用重组人肿瘤坏死因子α衍生物a的临床药代动力学 ,,.弓7一// 《癌症~2ooo年第19卷第12期l】37 注射用重组人肿瘤坏死因子()【衍生物a 的临床药代动力学 空蒸, 李端., 廖海, 招月好. 汪慧民, 崔案华, 简少文 管忠震 (1_中山医科大学肿瘤防治中内科,广东广lⅢ510060; 2中山医科大学肿瘤防治中心肿瘤研究所,广东广州510060) {} lo.-U 【摘要】目的:测定重组人肿瘤坏死因子d衍生物a(reeombinedhuii~rltumornecrosisfaetor-aderivative. ~TNF=Da)在人体内的药代动力学方法:6例肿瘤患者在50rain内静脉匀速滴注daTNF~Da4x10IU,用双抗体夹 心法侧定血清中daTNFaDa的浓度结果:血浆浓度.时间曲线呈二室模型,KKK..分别为1.73h～,554h～, 0.88h,:0.1057h±00125h,T1:153h±0.34h:表观分布容积V:0.623L?kg..;AUC:.452.4ng?h. L±103ng?h?L～.CL:1.096Lkg-1~绪论:rhTNFaDa是一个快速消除的药物,建议rhTNFaDa进一步临床研 究可考虑调整给药方案或制成缓释制剂. 关键词:肿瘤坏死因子;酶联免疫吸跗法 中图分类号:R9691文献标识码:A 药代动力学 文章编号 ^0巩肿珈善鲥 1000——467X(2000)12——1137..04 Pharmacokineticprofilesofintravenousadministrationofrecombinant humantumornecrosisfactor.Otderivative ⅡSu,LIAOHai.,WANGHui.ming,JIANShao-wen2,LIDuan2, ZHAOYue-hao,CUIJing-hua,GUANZhong—zhen 1.DepartmentofInternalMedicine,CancerCenter,SunYat-senUniversityof MedicalSciences,Guangzhou510060,P兄China 2.CancerInstitute.CancerCenter,Sun.Yat.senUniversitTof MedicalSciences.Guangzhou510060,R.China 【Abstract】Objecflve:ecurrentstudyWasdesignedtodeterminethepharmacokinetiesprofilesofrecombinent humantumorn~erosishc10rderivativefrhDa).Methods:Sixpatientswith∞ncwerereceived4x10IU 硎hl【intravenouslywithavolumctrlcinfusionpumpatconstantspecdin50rainSerumrhTNFhDa∞ncentrationWaS determinedbyenzyme—linkedimmun~arbentassaywithinstreptaviclirt-coatedmlcmtiterplates.Results: Two-compartmentmedelWaSusedtofittheplasmaconcentration-timepmfilo.PharmaeokineticparameterswereK:173 h-1,l:5.54h,K,0:0.鹋h一;/2.:01057h±0.0125h,Tl/2B:1.53h±0.34h;V:0.623L?kg;AUC:4524 ng.h.L±103nghL;CL1.096Lkg—ICoheir:rhTNhDaeliminatedquickly.Furtherinvestigation binedofaslow—relea吕igpreparationmaybeconsidered. Keywords:TuilllOrnecrosisfactor-derivative;Phannaeokinetics;Enzyme.1inkedimmuntmorbentaSS~V 文献报告肿瘤坏死因子(tum0rnecrosisfactor. derivative,TNFa)具有调节血管内皮细胞功能,诱导 收稿日期:2000—04—24;修回日期:200006—12 ★通讯作者:Tel:86—205222 抗病毒活性,刺激骨质吸收,血管生成和成纤维细胞 生长等多重活性.能专一杀伤肿瘤细胞而无碍于正 常细胞,但可引起疲倦,头疼,恶心,呕吐,腹泻,液体 潴留,尤其是寒战