DeJesus Edwin, Lalezari Jacob P, Osiyemi Olayemi O, Ruane Peter J, Ryan Robert, Kakuda Thomas N, Witek James
Orlando Immunology Center, Orlando, FL, USA.
Antivir Ther. 2010;15(5):711-20. doi: 10.3851/IMP1562.
A pharmacokinetic trial was conducted to evaluate the potential for once-daily etravirine in antiretroviral regimens without and with darunavir/ritonavir.
During this multicentre, open-label, Phase IIa trial, treatment-naive patients aged > or =18 years with HIV type-1 (HIV-1) received etravirine 400 mg once daily with tenofovir disoproxil fumarate/emtricitabine 300/200 mg once daily from days 1-14; on days 15-28, darunavir/ritonavir 800/100 mg once daily was added. On day 29, etravirine was discontinued and patients continued with the other medications to day 42. Serial blood sampling for etravirine pharmacokinetics was performed over 24 h on day 14 and 28; patients fasted for > or =10 h prior to these visits.
Of 23 enrolled patients (male 87%, Caucasian 39%), pharmacokinetic profiles for etravirine were available for 21 and 20 patients on day 14 and 28, respectively. The plasma concentration-time profile and pharmacokinetics for etravirine were unchanged with or without darunavir/ritonavir. The mean maximum plasma concentration (C(max)) was reached 4 h after administration and was 790 and 801 ng/ml on day 14 and 28, respectively; mean area under the plasma concentration-time curve (AUC) from before administration to 24 h after administration was 10,410 ngh/ml on day 14 and 10,720 ngh/ml on day 28. In a post-hoc analysis, etravirine C(max) was higher, minimum plasma concentration was lower and AUC was similar when compared with etravirine 200 mg twice daily.
Addition of darunavir/ritonavir to etravirine, all dosed once daily, did not have a clinically significant effect on the pharmacokinetics of etravirine. Findings support further investigation of etravirine 400 mg once daily in HIV-1-infected patients. (Trial registration number NCT00534352.).
开展了一项药代动力学试验，以评估每日一次依曲韦林在不含和含有达芦那韦/利托那韦的抗逆转录病毒治疗方案中的潜力。
在这项多中心、开放标签的IIa期试验中，年龄≥18岁的初治1型人类免疫缺陷病毒（HIV-1）感染患者从第1 - 14天接受每日一次400mg依曲韦林，同时每日一次300/200mg富马酸替诺福韦二吡呋酯/恩曲他滨；在第15 - 28天，添加每日一次800/100mg达芦那韦/利托那韦。在第29天，停用依曲韦林，患者继续服用其他药物至第42天。在第14天和第28天的24小时内进行依曲韦林药代动力学的系列血样采集；患者在这些访视前禁食≥10小时。
在23名入组患者（男性占87%，白种人占39%）中，分别有21名和20名患者在第14天和第28天获得了依曲韦林的药代动力学数据。无论是否使用达芦那韦/利托那韦，依曲韦林的血浆浓度 - 时间曲线和药代动力学均未改变。给药后4小时达到平均最大血浆浓度（C(max)），第14天和第28天分别为790和801ng/ml；给药前至给药后24小时的血浆浓度 - 时间曲线下平均面积（AUC）在第14天为10410ngh/ml，第28天为10720ngh/ml。在一项事后分析中，与每日两次200mg依曲韦林相比，依曲韦林的C(max)更高，最低血浆浓度更低，AUC相似。
每日一次给药的依曲韦林中添加达芦那韦/利托那韦，对依曲韦林的药代动力学没有临床显著影响。研究结果支持在HIV-1感染患者中进一步研究每日一次400mg依曲韦林。（试验注册号NCT00534352。）
