Departments of Biology and Public Health Sciences, University of Virginia, Charlottesville, Virginia, USA.
Division of Infectious Diseases and International Health, University of Virginia, Charlottesville, Virginia, USA.
J Pediatric Infect Dis Soc. 2021 Mar 26;10(2):104-111. doi: 10.1093/jpids/piaa024.
Individual pharmacokinetic variability is a driver of poor tuberculosis (TB) treatment outcomes. We developed a method for measurement of rifampin concentrations by urine colorimetry and a mobile phone photographic application to predict clinically important serum rifampin pharmacokinetic measurements in children treated for TB.
Among spiked urine samples, colorimetric assay performance was tested with conventional spectrophotometric and the mobile phone/light box methods under various environmental and biologic conditions. Urine rifampin absorbance (Abs) was then determined from timed specimens from children treated for TB in Tanzania, and compared to serum pharmacokinetic measurements collected throughout the dosing interval.
Both the mobile phone/light box and spectrophotometry demonstrated excellent correlation across a wide range of urine rifampin concentrations (7.8-1000 mg/L) in intra- and interday trials, 24-hour exposure to ambient light or darkness, and varying urinalysis profiles (all r ≥ 0.98). In 12 Tanzanian children, the urine mobile phone/light box measurement and serum peak concentration (Cmax) were significantly correlated (P = .004). Using a Cmax target of 8 mg/L, the area under the receiver operating characteristic curve was 80.1% (range, 47.2%-100%). A urine mobile phone/light box threshold of 50 Abs correctly classified all patients (n = 6) with serum measurements below target.
The urine colorimetry with mobile phone/light box assay accurately measured rifampin absorbance in varying environmental and biological conditions that may be observed clinically. Among children treated for TB, the assay was sensitive for detection of low rifampin serum concentrations. Future work will identify the optimal timing for urine collection, and operationalize use in TB-endemic settings.
个体药代动力学的变异性是导致结核病（TB）治疗效果不佳的一个因素。我们开发了一种通过尿比色法和手机拍照应用来测量利福平浓度的方法，以预测儿童结核病治疗中具有临床重要意义的血清利福平药代动力学测量值。
在加标尿液样本中，通过常规分光光度法和手机/灯箱法在各种环境和生物学条件下测试比色法的性能。然后，从坦桑尼亚接受结核病治疗的儿童的定时标本中测定尿液利福平吸光度（Abs），并与整个给药间隔内收集的血清药代动力学测量值进行比较。
在日内和日间试验中，手机/灯箱法和分光光度法在广泛的尿液利福平浓度（7.8-1000mg/L）范围内均表现出极好的相关性，尿液在 24 小时内暴露于环境光或黑暗中，以及不同的尿液分析谱（所有 r≥0.98）。在 12 名坦桑尼亚儿童中，尿液手机/灯箱测量值和血清峰浓度（Cmax）显著相关（P=0.004）。使用 8mg/L 的 Cmax 目标值，接受者操作特征曲线下面积为 80.1%（范围，47.2%-100%）。尿液手机/灯箱阈值为 50Abs 可正确分类所有（n=6）血清测量值低于目标值的患者。
在可能在临床上观察到的不同环境和生物学条件下，尿液比色法与手机/灯箱检测法准确地测量了利福平的吸光度。在接受结核病治疗的儿童中，该检测法对检测低血清利福平浓度敏感。未来的工作将确定最佳的尿液收集时间，并使其在结核病流行地区得到实际应用。
