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

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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。