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.

Levofloxacin pharmacokinetics in saliva as measured by a mobile microvolume UV spectrophotometer among people treated for rifampicin-resistant TB in Tanzania

“… 5–7 , 34 Anti-TB drug concentration testing in saliva complements other non-invasive tests, such as colorimetric assays recently developed in urine, which may expand access to personalized dosing not only for those people with TB distant from referral laboratories but also for populations such as children and/or those severely malnourished or with poor venous access where multiple blood draws will be relatively contraindicated or technically difficult. 35 , 36…”

Urine colorimetry for levofloxacin pharmacokinetics and personalized dosing in people with drug-resistant tuberculosis

“…We were successfully able to quantify levofloxacin in urine with a spectrophotometer using colorimetric principles. Although urine has been used for testing the presence of some first-line TB drugs using colorimetry, [ 11 , 14 ] to the best of our knowledge, this is the first time levofloxacin has been quantified in urine by colorimetric principles obtained from healthy participants after levofloxacin administration and patients living with HIV treated with levofloxacin for MDR-TB. The area under the ROC curve was >0.8 in the derivation as well as the validation study, which demonstrates that this assay performs well in predicting clinically important serum targets.…”

“…[ 9 , 10 ] Application of urine colorimetry for assessment of rifampicin PK/PD targets has been successful. [ 11 ] Thus, we modified a previously described assay for fluoroquinolone concentration measurement by urine colorimetry, examined its performance over a 24 h dosing interval of levofloxacin excretion, and assessed its ability to predict clinically relevant serum PK/PD targets from PLWH and taking levofloxacin for MDR-TB.…”

Practices of therapeutic drug monitoring in tuberculosis: an international survey

“…Our survey showed that progress in TDM is being made, with half of the survey participants using TDM. Cheaper and easy to use assays [9][10][11], clinical guidelines [2][3][4] and laboratory quality control standards [12] are all increasing in availability. However, the main challenge is a lack of widespread information about TDM, with progress being recognised by participants who look towards guidelines and research when performing TDM.…”