氧化苦参碱与拉米夫定在beagle犬体内的药物动力学相互呢作用研究.docVIP

PAGE PAGE 2 基金项目：863 Program，No. 2004AA2Z3100 作者简介：刘晓红 女 沈阳药科大学 讲师 博士 email：lvj221@163.com ※通讯作者： 何仲贵 男 教授 Tel：(024Email： HYPERLINK mailto:hezhonggui@ hezhonggui@ 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-dose pharmacokinetics of lamivudine and oxymatrine administrated alone and in combination to beagle dogs Xiaohong Liu, Yinghua Sun, Jin Sun, Zhonggui He※(School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China ABSTRACT: OBJECTIVE To evaluate the single-dose pharmacokinetic interaction of lamivudine and oxymatrine in combination to beagle dogs, both of drugs which are active against hepatitis B virus and which exert synergetic antiviral effect by co-administration. METHODS A randomized 3 way crossover-Latin square experiment was designed. Twelve healthy adult male beagle dogs were divided into two groups. Six dogs were randomly intravenously administrated with lamivudine (2.5 mg/kg) and oxymatrine (15 mg/kg) alone and in combination, while the other six dogs were orally administrated with lamivudine (5 mg/kg) and oxymatrine (30 mg/kg) alone and in combination. RESULTS Simultaneous oral treatment with lamivudine and oxymatrine did not significantly affect the in vivo pharmacokinetic behavior of the two drugs, even including matrine, the active metabolite of oxymatrine. Furthermore, the main pharmacokinetic parameters of three compounds were not significantly influenced by the simultaneous intravenous administration of lamivudine and oxymatrine. CONCLUSIONS The concomitant oral or intravenous use of lamivudine and oxymatrine did not lead to significant pharmacokinetic interactions in beagle dogs. Moreover, the present study pr