Common clinical conditions - age, low BMI, ritonavir use, mild renal impairment - affect tenofovir pharmacokinetics in a large cohort of HIV-infected women.
Common clinical conditions - age, low BMI, ritonavir use, mild renal impairment - affect tenofovir pharmacokinetics in a large cohort of HIV-infected women.
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DOI：
10.1097/qad.0000000000000033
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发表时间：
2014-01-02
期刊：
影响因子：
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通讯作者：
Gandhi M
中科院分区：
文献类型：
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作者：
Baxi SM;Greenblatt RM;Bacchetti P;Scherzer R;Minkoff H;Huang Y;Anastos K;Cohen M;Gange SJ;Young M;Shlipak MG;Gandhi M
替诺福韦通常用于艾滋病毒治疗和预防，但在现实环境中与替诺福韦暴露相关的因素尚不清楚。在一个大型、多样化的艾滋病毒感染妇女队列中，对替诺福韦进行了24小时稳态的强化药代动力学（PK）研究，并对影响暴露的因素（通过时间下浓度曲线面积评估，AUCs）进行了强化的24小时PK采样，确定了接受替诺福韦治疗的艾滋病毒感染妇女（n=101）。收集有关种族/民族、年龄、外源性类固醇使用、月经周期阶段、伴随用药、消遣性药物和/或烟草、肝肾功能、体重和体重指数（BMI）的数据。采用前向逐步选择的多变量模型确定了与AUC影响相关的因素。开始使用替诺福韦前的肾小球滤过率（GFR）通过CKD-EPI方程使用肌酐和胱抑素- c测量来估计。替诺福韦auc的中位数（范围）为3350 (1031 - 13911)ng x h/mL。较高的auc与同时使用利托那韦（1.33倍增加，p 0.002）、年龄增加（每10年增加1.21倍，p=0.0007）和BMI下降（每BMI下降10%增加1.04倍）相关。当使用胱他汀- c测量计算GFR时，替诺福韦开始使用前轻度肾功能不全与随后较高的暴露相关（当替诺福韦开始使用前GFR <70mL/min时增加1.35倍，p=0.0075）。根据胱抑素C估计，在替诺福韦开始使用前，同时使用利托那韦、年龄增加、BMI下降和GFR降低，都与不同hiv感染妇女队列中替诺福韦暴露量升高有关。治疗艾滋病毒感染妇女的临床医生在开替诺福韦处方时，应了解影响替诺福韦暴露的常见临床情况。
Tenofovir is used commonly in HIV treatment and prevention settings, but factors that correlate with tenofovir exposure in real-world setting are unknown. Intensive pharmacokinetic (PK) studies of tenofovir in a large, diverse cohort of HIV-infected women over 24-hours at steady-state were performed and factors that influenced exposure (assessed by areas-under-the-time-concentration curves, AUCs) identified HIV-infected women (n=101) on tenofovir-based therapy underwent intensive 24-hour PK sampling. Data on race/ethnicity, age, exogenous steroid use, menstrual cycle phase, concomitant medications, recreational drugs and/or tobacco, hepatic and renal function, weight and body mass index (BMI) were collected. Multivariable models using forward stepwise selection identified factors associated with effects on AUC. Glomerular filtration rates (GFR) prior to starting tenofovir were estimated by the CKD-EPI equation using both creatinine and cystatin-C measures The median (range) of tenofovir AUCs was 3350 (1031–13,911) ng x h/mL. Higher AUCs were associated with concomitant ritonavir use (1.33-fold increase, p 0.002), increasing age (1.21-fold increase per decade, p=0.0007) and decreasing BMI (1.04-fold increase per 10% decrease in BMI). When GFR was calculated using cystatin-C measures, mild renal insufficiency prior to tenofovir initiation was associated with higher subsequent exposure (1.35-fold increase when pre-tenofovir GFR <70mL/min, p=0.0075). Concomitant ritonavir use, increasing age, decreasing BMI and lower GFR prior to tenofovir initiation as estimated by cystatin C were all associated with elevated tenofovir exposure in a diverse cohort of HIV-infected women. Clinicians treating HIV-infected women should be aware of common clinical conditions that affect tenofovir exposure when prescribing this medication.