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ID:28918090
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时间:2018-12-15
《氧化苦参碱与拉米夫定在beagle犬体内的药物动力学相互作用研究》由会员上传分享,免费在线阅读,更多相关内容在学术论文-天天文库。
1、氧化苦参碱与拉米夫定在Beagle犬体内的药物动力学相互作用研究刘晓红孙英华孙进何仲贵※(沈阳药科大学药学院生物药剂学研究室,辽宁沈阳,110016)摘要目的:评价氧化苦参碱(OM)和拉米夫定(3TC)在体内的药物动力学相互作用,为指导临床用药提供理论依据。方法:同时灌胃或静注给予Beagle犬单剂量OM和3TC,采用固相萃取(SPE)和HPLC-UV法分析不同时刻Beagle犬血药浓度。结果:3TC和OM联合用药后不改变二者在Beagle犬的体内药动学参数,也不改变OM代谢产物苦参碱(M)的生物转化率和体内药动学参数(p>0.05)。结论:3TC和OM配
2、伍使用后在Beagle犬体内未发生药物动力学相互作用。关键词:氧化苦参碱;苦参碱;拉米夫定;药物相互作用Single-dosepharmacokineticsoflamivudineandoxymatrineadministratedaloneandincombinationtobeagledogsXiaohongLiu,YinghuaSun,JinSun,ZhongguiHe※(SchoolofPharmacy,ShenyangPharmaceuticalUniversity,Shenyang110016,China)ABSTRACT:OBJECTIVE
3、Toevaluatethesingle-dosepharmacokineticinteractionoflamivudineandoxymatrineincombinationtobeagledogs,bothofdrugswhichareactiveagainsthepatitisBvirusandwhichexertsynergeticantiviraleffectbyco-administration.METHODSArandomized3waycrossover-Latinsquareexperimentwasdesigned.Twelveheal
4、thyadultmalebeagledogsweredividedintotwogroups.Sixdogswererandomlyintravenouslyadministratedwithlamivudine(2.5mg/kg)andoxymatrine(15mg/kg)aloneandincombination,whiletheothersixdogswereorallyadministratedwithlamivudine(5mg/kg)andoxymatrine(30mg/kg)aloneandincombination.RESULTSSimul
5、taneousoraltreatmentwithlamivudineandoxymatrinedidnotsignificantlyaffecttheinvivopharmacokineticbehaviorofthetwodrugs,evenincludingmatrine,theactivemetaboliteofoxymatrine.Furthermore,themainpharmacokineticparametersofthreecompoundswerenotsignificantlyinfluencedbythesimultaneousint
6、ravenousadministrationoflamivudineandoxymatrine.CONCLUSIONSTheconcomitantoralorintravenoususeoflamivudineandoxymatrinedidnotleadtosignificantpharmacokineticinteractionsinbeagledogs.Moreover,thepresentstudyprovidestheinvivopharmacokineticbasisforsupportingtherecentclinicalpractices
7、inChinathatnodosageadjustmentisneededwhenlamivudineandoxymatrineareco-administrated.Keywords:Oxymatrine;Lamivudine;pharmacokineticinteraction.拉米夫定(3TC)为胞嘧啶核苷类似物,属于RNA逆转录酶抑制剂,对乙肝病毒(HBV)有抑制作用[1,2]。然而其长期应用会产生耐药现象,影响其疗效[3,4]。氧化苦参碱(OM)可直接抗HBV,并且具有稳定肝细胞膜、阻断肝细胞凋亡等作用[5]。临床研究已经表明[6-8],二者联合
8、应用,可协同提高疗效,缩短疗程,是目前治疗慢性乙型肝炎的较好选择。
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