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首页> 外文期刊>AIDS Research and Human Retroviruses >Factors Associated with Daily Tenofovir Exposure in Thai Subjects Taking Combination Antiretroviral Therapy
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Factors Associated with Daily Tenofovir Exposure in Thai Subjects Taking Combination Antiretroviral Therapy

机译：联合抗逆转录病毒疗法在泰国受试者中与每日替诺福韦暴露相关的因素

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摘要

Tenofovir (TFV) exposure is associated with antiretroviral efficacy and risk of kidney disease. There is evidence of high interindividual variability of the pharmacokinetics of TFV. The effect of several clinical conditions on the pharmacokinetics of TFV has been observed and may partly explain its variability. We assessed factors influencing the pharmacokinetics of TFV in Thai patients. Thirty participants (50% female) taking efavirenz- or ritonavir-boosted protease inhibitor-based regimens were investigated. Intensive pharmacokinetic sampling was performed over 24 h. Multivariate geometric mean regression models adjusted for covariates with p <= 0.2 in univariate analysis were developed. The median age was 41 years. Five participants [three taking a protease inhibitor (PI) and two taking efavirenz (EFV)] had mild renal dysfunction [estimated glomerular filtration rate (eGFR) 60-90 ml/min/1.73 m(2); range 72-89]. TFV AUC(0-24) was 23% (95% CI 1-49%; p=0.04) higher in those taking PI vs. EFV, 39% (95% CI 5-84%; p=0.02) higher in those with mild renal dysfunction, and reduced by 16% (95% CI 5-26%; p=0.008) with each 10 kg body weight increase, after adjusting for sex and duration of TFV exposure. In PI-treated subjects TFV AUC(0-24) increased by 3% (0.3-6%; p=0.03) for each mg center dot h/liter increase in ritonavir (RTV) AUC(0-24) after adjusting for sex, weight, mild renal impairment, and proximal renal tubular dysfunction. Significantly higher TFV exposures were independently associated with PI regimens, mild renal impairment, lower body weight, and increasing RTV AUC(0-24). Clinicians should be aware of the effect of these factors on TFV exposure when this drug is prescribed.
机译：替诺福韦（TFV）暴露与抗逆转录病毒药效和患肾脏疾病的风险有关。有证据表明，TFV的药代动力学存在很大的个体差异。已经观察到几种临床状况对TFV药代动力学的影响，并可能部分解释其变异性。我们评估了影响泰国患者TFV药代动力学的因素。研究了三十名接受依非韦伦或利托那韦增强蛋白酶抑制剂治疗方案的参与者（女性占50％）。在24小时内进行密集的药代动力学采样。建立了在单变量分析中针对p <= 0.2进行协变量调整的多元几何均值回归模型。中位年龄为41岁。五名参与者[三名服用蛋白酶抑制剂（PI），两名服用依非韦伦（EFV）]患有轻度肾功能不全[估计肾小球滤过率（eGFR）60-90 ml / min / 1.73 m（2）;范围72-89]。服用PI的患者TFV AUC（0-24）比EFV高23％（95％CI 1-49％; p = 0.04），与EFV相比高39％（95％CI 5-84％; p = 0.02）在调整了性别和TFV暴露持续时间后，每增加10公斤体重，其轻度肾功能不全就会下降16％（95％CI 5-26％; p = 0.008）。在接受性别调整后，利托那韦（RTV）AUC（0-24）每增加1 mg中心点h /升，在PI治疗的受试者中TFV AUC（0-24）增加3％（0.3-6％; p = 0.03） ，体重，轻度肾功能不全和近端肾小管功能障碍。明显更高的TFV暴露与PI方案，轻度肾功能不全，体重减轻和RTV AUC（0-24）增加独立相关。开药后，临床医生应注意这些因素对TFV暴露的影响。

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