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.doc

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，110016Single-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 provides the in vivo pharmacokinetic basis for supporting the recent clinical practices in China that no dosage adjustment is needed when lamivudine and oxymatrine are co-administrated. Keywords: Oxymatrine; Lamivudine; pharmacokinetic interaction. 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。但两药以及OM的代谢产物——苦参碱（M