Blum M Robert, Chittick Gregory E, Begley John A, Zong Jian
Gilead Sciences, Inc, 4 University Place, 4611 University Drive, Durham, NC 27709, USA.
J Clin Pharmacol. 2007 Jun;47(6):751-9. doi: 10.1177/0091270007300951.
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 emtricitabine qd for 7 days, 300 mg tenofovir 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.
已获批的抗逆转录病毒药物恩曲他滨和替诺福韦酯富马酸盐，被认为是固定剂量复方产品的良好候选药物，该复方产品可每日一次（qd）作为单一药丸给药，从而简化现有治疗方案并提高患者依从性。由于这两种药物均主要经肾脏排泄，因此在19名健康志愿者中开展了一项随机、三交叉研究，以正式评估单独给药和联合给药（即，恩曲他滨200 mg qd给药7天、替诺福韦酯富马酸盐300 mg qd给药7天，以及恩曲他滨200 mg加替诺福韦酯富马酸盐300 mg qd给药7天）时的潜在药代动力学相互作用，各治疗组之间不进行洗脱期。与单独使用每种药物相比，恩曲他滨和替诺福韦（以替诺福韦酯富马酸盐形式）联合给药时的稳态药代动力学参数（AUC(tau)、C(max)和C(min)）基本相当，这为将这些产品组合制成恩曲他滨/替诺福韦酯富马酸盐固定剂量片剂提供了药代动力学依据。
