Faculty of Medicine, Imperial College, London, UK Department of HIV and Genitourinary Medicine, Imperial College Healthcare NHS Trust St Mary's Hospital, London, UK
Department of Clinical and Molecular Pharmacology, University of Liverpool, Liverpool, UK.
J Antimicrob Chemother. 2014 Jun;69(6):1642-7. doi: 10.1093/jac/dku018. Epub 2014 Feb 11.
Pharmacokinetic parameters following modifications to antiretroviral therapy and sanctuary site exposure are often unknown for recently licensed antiretrovirals. We assessed plasma, CSF and seminal plasma (SP) exposure of rilpivirine after switching from nevirapine.
HIV-infected male subjects receiving tenofovir/emtricitabine/nevirapine (245/200/400 mg) once daily switched to tenofovir/emtricitabine/rilpivirine (245/200/25 mg) once daily for 60 days when CSF and semen samples were collected. Mean and individual plasma concentrations of nevirapine and rilpivirine were compared with the proposed plasma target concentration for nevirapine (3000 ng/mL) and the protein binding-adjusted EC90 for rilpivirine (12.1 ng/mL). Mean rilpivirine CSF and SP concentrations were calculated and individual values compared with the EC50 and EC90 for wild-type virus (0.27 and 0.66 ng/mL, respectively).
Of 13 subjects completing study procedures including CSF examination, 8 provided seminal samples. By day 3, the mean plasma rilpivirine trough concentration was 29.7 ng/mL (95% CI: 23.8-37). No patient presented rilpivirine plasma concentrations under the proposed threshold. The mean rilpivirine concentration in CSF was 0.8 ng/mL (95% CI: 0.7-1.0), representing a CSF : plasma ratio of 1.4%, with concentrations above the EC90 in 85% (11/13) of patients. In SP, the mean rilpivirine concentration was 4.9 ng/mL (95% CI: 3.3-7.2), representing an SP : plasma ratio of 9.5%, with all concentrations above the EC90.
Switching from nevirapine- to rilpivirine-containing antiretroviral therapy was safe and well tolerated, with plasma rilpivirine concentrations above the protein binding-adjusted EC90 in all subjects. Rilpivirine concentrations were always above the EC50 in the CSF and the EC90 in SP.
对于最近获得批准的抗逆转录病毒药物，改变抗逆转录病毒治疗方案和避难所部位暴露后，药代动力学参数通常未知。我们评估了利匹韦林替代奈韦拉平后的血浆、CSF 和精液（SP）暴露情况。
正在接受替诺福韦/恩曲他滨/奈韦拉平（245/200/400 mg）每日一次治疗的 HIV 感染男性受试者，当采集 CSF 和精液样本时，转为替诺福韦/恩曲他滨/利匹韦林（245/200/25 mg）每日一次治疗，共 60 天。比较奈韦拉平和利匹韦林的平均和个体血浆浓度与建议的奈韦拉平血浆靶浓度（3000 ng/mL）和利匹韦林蛋白结合调整的 EC90（12.1 ng/mL）。计算了平均利匹韦林 CSF 和 SP 浓度，并将个体值与野生型病毒的 EC50 和 EC90 进行了比较（分别为 0.27 和 0.66 ng/mL）。
13 名完成包括 CSF 检查在内的研究程序的受试者中，8 名提供了精液样本。到第 3 天，利匹韦林的平均血浆谷浓度为 29.7 ng/mL（95%CI：23.8-37）。没有患者的利匹韦林血浆浓度低于建议的阈值。CSF 中的平均利匹韦林浓度为 0.8 ng/mL（95%CI：0.7-1.0），代表 1.4%的 CSF:血浆比，85%（11/13）的患者浓度高于 EC90。在 SP 中，利匹韦林的平均浓度为 4.9 ng/mL（95%CI：3.3-7.2），代表 9.5%的 SP:血浆比，所有浓度均高于 EC90。
从奈韦拉平到含利匹韦林的抗逆转录病毒治疗的转换是安全且耐受良好的，所有受试者的血浆利匹韦林浓度均高于蛋白结合调整的 EC90。CSF 和 SP 中的利匹韦林浓度始终高于 EC50 和 EC90。
