Pharmacokinetic profile and safety of 150 mg of maraviroc dosed with 800/100 mg of darunavir/ritonavir all once daily, with and without nucleoside analogues, in HIV-infected subjects.
Pharmacokinetic profile and safety of 150 mg of maraviroc dosed with 800/100 mg of darunavir/ritonavir all once daily, with and without nucleoside analogues, in HIV-infected subjects.
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在 HIV 感染受试者中，每日一次服用 150 mg 马拉韦罗与 800/100 mg 地芦那韦/利托那韦（含或不含核苷类似物）的药代动力学特征和安全性。
DOI：
10.1093/jac/dkt006
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Mora-Peris B
中科院分区：
文献类型：
--
作者：
Mora-Peris B
研究背景每天一次的核苷保留联合抗逆转录病毒治疗方案是治疗HIV感染的有吸引力的选择。然而，这样的方案的药代动力学曲线往往没有established. MethodsHIV感染的受试者接受245/200毫克的替诺福韦/恩曲他滨加800/100毫克的地瑞那韦/利托那韦每天一次与血浆HIV RNA <50拷贝/mL是合格的。在第1天（第1阶段），每天添加150 mg马拉韦罗，在第11天（第2阶段），停用替诺福韦/恩曲他滨。在稳态（第10天和第20天）时，进行密集的药代动力学采样。我们评估了（i）maraviroc谷浓度（Ctrough）和平均浓度（Cavg）分别<25和<75 ng/mL的受试者数量;（ii）第2阶段与第1阶段药代动力学参数的几何平均值（GM）比;以及（iii）与总maraviroc暴露相关的因素。在3名受试者中，马拉韦罗C谷和Cavg分别<25和<75 ng/mL（Cavg，68 ng/mL和C谷，14和21 ng/mL）。尽管无统计学显著性，但在第2阶段观察到马拉韦罗、地瑞那韦和利托那韦浓度低于第1阶段的趋势;第1阶段和第2阶段的马拉韦罗总暴露量分别为3579 ng·h/mL（95% CI：2983-4294）和2996 ng·h/mL（95% CI：2374-3782），GM比值为0.84（95% CI：0.67-1.05）。 只有利托那韦总暴露量与马拉韦罗总暴露量显著相关（P= 0.049; 95%CI：0.01-0.91）。 No clinical safety concerns were observed.ConclusionsWithin this novel nucleoside-sparing regime，maraviroc exposure is dependent on ritonavir exposure，which was slightly reduced in the absence of tenofovir/emtricitabine.
BackgroundOnce-daily nucleoside-sparing combination antiretroviral therapy regimens are attractive options for the treatment of HIV infection. However, the pharmacokinetic profiles of such regimens are often not established.MethodsHIV-infected subjects receiving 245/200 mg of tenofovir/emtricitabine plus 800/100 mg of darunavir/ritonavir once daily with plasma HIV RNA <50 copies/mL were eligible. On day 1 (period 1), 150 mg of maraviroc daily was added and on day 11 (period 2), tenofovir/emtricitabine discontinued. At steady-state (days 10 and 20), intensive pharmacokinetic sampling was undertaken. We assessed (i) the number of subjects with trough (Ctrough) and average (Cavg) maraviroc concentrations <25 and <75 ng/mL, respectively; (ii) geometric mean (GM) ratios for pharmacokinetic parameters for period 2 versus period 1; and (iii) factors associated with total maraviroc exposure.ResultsEleven subjects completed the study procedures (mean age 49 years; range 35–59 years). In three subjects, maravirocCtroughandCavgwere <25 and <75 ng/mL, respectively (Cavg, 68 ng/mL andCtrough, 14 and 21 ng/mL). Although not statistically significant, a trend was observed towards lower maraviroc, darunavir and ritonavir concentrations in period 2 versus period 1; total maraviroc exposure was 3579 ng· h/mL (95% CI: 2983–4294) and 2996 ng· h/mL (95% CI: 2374–3782) in periods 1 and 2, respectively, and the GM ratio was 0.84 (95% CI: 0.67–1.05). Only total ritonavir exposure was significantly associated with total maraviroc exposure (P= 0.049; 95% CI: 0.01–0.91). No clinical safety concerns were observed.ConclusionsWithin this novel nucleoside-sparing regimen, maraviroc exposure is dependent on ritonavir exposure, which was slightly reduced in the absence of tenofovir/emtricitabine.
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