Steady-state pharmacokinetics of emtricitabine and tenofovir disoproxil fumarate administered alone and in combination in healthy volunteers
Steady-state pharmacokinetics of emtricitabine and tenofovir disoproxil fumarate administered alone and in combination in healthy volunteers
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DOI：
10.1177/0091270007300951
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发表时间：
2007-06-01
影响因子：
2.9
通讯作者：
Zong, Jian
中科院分区：
文献类型：
--
作者：
Blum, M. Robert;Chittick, Gregory E.;Zong, Jian
已批准的抗逆转录病毒药物恩曲他滨和富马酸替诺福韦酯被认为是固定剂量复方制剂的良好候选药物，可以作为每日一次（qd）的单一药丸给药，从而简化现有的治疗方案并促进患者的依从性。由于这两种药物均经肾脏广泛消除，因此在19名健康志愿者中进行了一项随机、3向交叉研究，以正式评价两种药物单独和联合给药时的潜在药代动力学相互作用（即恩曲他滨200 mg qd 7天，富马酸替那福韦二异丙酯300 mg qd 7天，和200 mg恩曲他滨加300 mg富马酸替诺福韦酯qd，持续7天），治疗之间没有洗脱。恩曲他滨和替诺福韦（作为富马酸替诺福韦酯）联合给药的稳态药代动力学参数（AUC（tau）C-max和C-min）与每种药物单独给药基本相同，这为将这些产品联合用于恩曲他滨/富马酸替诺福韦酯固定剂量片剂提供了药代动力学依据，
The approved antiretroviral drugs, emtricitabine and tenofovir disoproxil fumarate, were considered good candidates for a fixed-dose combination product that could be administered as a single pill once daily (qd), thereby simplifying existing treatment regimens and promoting patient adherence. As both drugs are extensively renally eliminated, a randomized, 3-way crossover study was conducted in 19 healthy volunteers to formally evaluate the potential pharmacokinetic interaction when the drugs are administered alone and together (ie, 200 mg erntricitabine qd for 7 days, 300 mg tenafovir disoproxil fumarate qd for 7 days, and 200 mg emtricitabine plus 300 mg tenofovir disoproxil fumarate qd for 7 days) with no washout between treatments. Steady-state pharmacokinetic parameters (AUC(tau) C-max, and C-min) of emtricitabine and tenofovir (as tenofovir disoproxil fumarate) in combination were essentially equivalent versus each drug alone, providing a pharmacokinetic rationale for combining these products in emtricitabine/tenofovir disoproxil fumarate fixed-dose tablets,