Determination of Rifampin Concentrations by Urine Colorimetry and Mobile Phone Readout for Personalized Dosing in Tuberculosis Treatment

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: colorimetry; pediatric tuberculosis; pharmacokinetics; rifampin; therapeutic drug monitoring.

© The Author(s) 2020. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Figures

Figure 1.

Mobile phone/light box apparatus.

Figure 2.

Calibration curve for the urine colorimetric assay using the mobile phone/light box (A) and conventional spectrophotometer (B) to measure absorbance (Abs) in stock urine samples.

Figure 3.

Serum rifampin concentrations over time among children treated for tuberculosis in Tanzania.

Figure 4.

Correlation between peak serum rifampin concentration (Cmax) and the urine colorimetric assay with absorbance (Abs) measured by mobile phone/light box (A) and conventional spectrophotometry (B), and correlation between rifampin area under the concentration–time curve from 0 to 24 hours (AUC0–24) and absorbance measured by mobile phone/light box (C) and conventional spectrophotometry (D) among children treated for tuberculosis in Tanzania.

Figure 5.

Urine assay results among children treated for tuberculosis in Tanzania with peak serum concentration (Cmax) of rifampin > 8 or ≥ 8 mg/L (A) and with rifampin area under the curve from 0 to 24 hours (AUC0–24) > 35 or ≥ 35 mg × hour/L (B), using the mobile phone/light box to measure absorbance (Abs).

Figure 6.

Receiver operating characteristic (ROC) curves for the mobile phone/light box assay to identify patients with peak serum rifampin concentration (Cmax) < 8 mg/L (A), and patients with area under the rifampin serum concentration curve from 0 to 24 hours (AUC0–24) < 35 mg × hour/L (B) among children treated for tuberculosis in Tanzania.