Age-Related Changes in Plasma Concentrations of the HIV Protease Inhibitor Lopinavir
Age-Related Changes in Plasma Concentrations of the HIV Protease Inhibitor Lopinavir
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DOI：
10.1089/aid.2009.0154
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发表时间：
2010-06-01
影响因子：
1.5
通讯作者：
Flexner, Charles
中科院分区：
文献类型：
--
作者：
Crawford, Keith W.;Spritzler, John;Flexner, Charles
治疗艾滋病毒疾病的高效抗逆转录病毒疗法的出现大大延长了艾滋病毒感染者的寿命，导致老年艾滋病毒感染者人数不断增加。抗逆转录病毒药物在人群中的有效性和安全性是重要的关注点。评估老年患者抗逆转录病毒药代动力学的研究相对较少。 37 名年龄 18-30 岁的受试者和 40 名年龄 45-79 岁的受试者，未接受过抗逆转录病毒治疗，接受洛匹那韦/利托那韦 (400/100) bid、恩曲他滨 200 mg qd 和司他夫定 40 mg bid。 44 名受试者在 24、36 和 96 周时收集了洛匹那韦的谷浓度。在第24周，年龄较大与洛匹那韦谷浓度较高相关，并且在评估所有时间点时观察到年龄较大与洛匹那韦谷浓度较高相关的趋势。在年轻队列中，在进行两次或多次测量的受试者中，随着时间的推移，受试者体内洛匹那韦谷浓度有增加的趋势。使用非线性、混合效应群体药代动力学模型，调整依从性后，年龄与洛匹那韦清除率呈负相关。通过患者自我报告评估依从性；老年患者比年轻患者错过的剂量更少 (p = 0.02)。两个年龄组之间未观察到 3-4 级毒性差异。老年患者洛匹那韦谷浓度较高，洛匹那韦清除率可能降低。随着艾滋病毒感染人群的老龄化以及老年人在新诊断中所占比例的增加，抗逆转录病毒药物药代动力学中与年龄相关的变化可能变得越来越重要。
The advent of highly active antiretroviral therapy in the treatment of HIV disease has substantially extended the lifespan of individuals infected with HIV resulting in a growing population of older HIV-infected individuals. The efficacy and safety of antiretroviral agents in the population are important concerns. There have been relatively few studies assessing antiretroviral pharmacokinetics in older patients. Thirty-seven subjects aged 18-30 years and 40 subjects aged 45-79 years, naive to antiretroviral therapy, received lopinavir/ritonavir (400/100) bid, emtricitibine 200 mg qd, and stavudine 40 mg bid. Trough lopinavir concentrations were available for 44 subjects, collected at 24, 36, and 96 weeks. At week 24, older age was associated with higher lopinavir trough concentrations, and a trend was observed toward older age being associated with higher lopinavir trough concentrations when all time points were evaluated. In the young cohort, among subjects with two or more measurements, there was a trend toward increasing intrasubject trough lopinavir concentrations over time. Using a nonlinear, mixed-effects population pharmacokinetic model, age was negatively associated with lopinavir clearance after adjusting for adherence. Adherence was assessed by patient self-reports; older patients missed fewer doses than younger patients (p = 0.02). No difference in grade 3-4 toxicities was observed between the two age group. Older patients have higher trough lopinavir concentrations and likely decreased lopinavir clearance. Age-related changes in the pharmacokinetics of antiretroviral drugs may be of increasing importance as the HIV-infected population ages and as older individuals comprise an increasing proportion of new diagnoses.