Gilead Sciences, Inc., Foster City, CA.
J Acquir Immune Defic Syndr. 2018 Aug 1;78(4):465-472. doi: 10.1097/QAI.0000000000001699.
Tenofovir alafenamide (TAF), a prodrug of the nucleotide analogue tenofovir (TFV), is an antiretroviral (ARV) agent approved either as a complete regimen [elvitegravir/cobicistat/emtricitabine (F)/TAF, rilpivirine/F/TAF, bictegravir/F/TAF], or for use with other ARVs (F/TAF), for treatment of HIV. TAF is a substrate of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) transporters. Disposition of TAF may be altered by comedications that can inhibit or induce P-gp or BCRP transporters. The effects of ARVs on the pharmacokinetics of TAF were evaluated in 3 studies.
Healthy participants received TAF administered alone or with rilpivirine in study 1, with dolutegravir, ritonavir-boosted atazanavir (ATV + RTV), lopinavir (LPV/RTV), or darunavir (DRV + RTV) in study 2, and with the pharmacokinetic enhancer cobicistat or efavirenz in study 3.
Across the 3 studies, 98 participants received treatment with TAF and a coadministered agent (n = 10-34/cohort). All study treatments were well tolerated. TAF and TFV exposures were unaffected after co-administration with rilpivirine and dolutegravir. Coadministration with P-gp/BCRP inhibitors such as cobicistat or PI-based regimens (ATV + RTV, LPV/r, or DRV + RTV) resulted in a range of 6%-183% increases in TAF and 105%-316% increases in TFV exposure, whereas coadministration with a P-gp inducer, efavirenz, resulted in a 15%-24% decrease in TAF and TFV exposure.
Evaluation of the drug interaction between TAF and other commonly prescribed boosted and unboosted ARVs provides characterization of the susceptibility of TAF and/or TFV pharmacokinetics to inhibitors or inducers of P-gp/BCRP transporters.
替诺福韦艾拉酚胺（TAF）是核苷酸类似物替诺福韦（TFV）的前药，是一种抗逆转录病毒（ARV）药物，已被批准作为完整方案[依维莫司/考比司他/恩曲他滨（F）/TAF、利匹韦林/F/TAF、比克替拉韦/F/TAF]或与其他 ARV 联合使用（F/TAF），用于治疗 HIV。TAF 是 P-糖蛋白（P-gp）和乳腺癌耐药蛋白（BCRP）转运体的底物。可抑制或诱导 P-gp 或 BCRP 转运体的合并用药可能会改变 TAF 的处置。在 3 项研究中评估了 ARV 对 TAF 药代动力学的影响。
健康参与者在研究 1 中单独接受 TAF 或与利匹韦林联合治疗，在研究 2 中接受多替拉韦、利托那韦增强的阿扎那韦（ATV+RTV）、洛匹那韦/利托那韦（LPV/RTV）或达芦那韦（DRV+RTV）联合治疗，在研究 3 中接受药代动力学增强剂考比司他或依非韦伦联合治疗。
在 3 项研究中，98 名参与者接受了 TAF 联合其他合用药物的治疗（n=10-34/队列）。所有研究治疗均耐受良好。与利匹韦林和多替拉韦合用时，TAF 和 TFV 暴露不受影响。与 P-gp/BCRP 抑制剂（如考比司他或基于 PI 的方案[ATV+RTV、LPV/r 或 DRV+RTV]）联合使用可导致 TAF 暴露增加 6%-183%，TFV 暴露增加 105%-316%，而与 P-gp 诱导剂依非韦伦联合使用可导致 TAF 和 TFV 暴露减少 15%-24%。
评估 TAF 与其他常用的增强和未增强的 ARV 之间的药物相互作用，为 TAF 和/或 TFV 药代动力学对 P-gp/BCRP 转运体抑制剂或诱导剂的敏感性提供了特征。
