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Urine colorimetry to detect Low rifampin exposure during tuberculosis therapy: a proof-of-concept study
Journal article   Open access   Peer reviewed

Urine colorimetry to detect Low rifampin exposure during tuberculosis therapy: a proof-of-concept study

Isaac Zentner, Hans P Schlecht, Lorna Khensouvann, Neo Tamuhla, Michele Kutzler, Vijay Ivaturi, Jotam G Pasipanodya, Tawanda Gumbo, Charles A Peloquin, Gregory P Bisson, …
BMC infectious diseases, v 16(1), pp 242-242
01 Jun 2016
DOI: https://doi.org/10.1186/s12879-016-1576-1
PMID: 27250739
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://doi.org/10.1186/s12879-016-1576-1View
Published, Version of Record (VoR)CC BY V4.0,  Open

Abstract

Adult Antitubercular Agents - analysis Antitubercular Agents - therapeutic use Antitubercular Agents - urine Botswana Colorimetry - methods Cross-Over Studies Dose-Response Relationship, Drug Drug Monitoring - methods Female Healthy Volunteers Humans Male Rifampin - analysis Rifampin - therapeutic use Rifampin - urine ROC Curve Sensitivity and Specificity Specimen Handling Tuberculosis - drug therapy Tuberculosis - urine Urinalysis - methods
The cost and complexity of current approaches to therapeutic drug monitoring during tuberculosis (TB) therapy limits widespread use in areas of greatest need. We sought to determine whether urine colorimetry could have a novel application as a form of therapeutic drug monitoring during anti-TB therapy. Among healthy volunteers, we evaluated 3 dose sizes of rifampin (150 mg, 300 mg, and 600 mg), performed intensive pharmacokinetic sampling, and collected a timed urine void at 4 h post-dosing. The absorbance peak at 475 nm was measured after rifamycin extraction. The optimal cutoff was evaluated in a study of 39 HIV/TB patients undergoing TB treatment in Botswana. In the derivation study, a urine colorimetric assay value of 4.0 × 10(-2) Abs, using a timed void 4 h after dosing, demonstrated a sensitivity of 92 % and specificity of 60 % to detect a peak rifampin concentration (Cmax) under 8 mg/L, with an area under the ROC curve of 0.92. In the validation study, this cutoff was specific (100 %) but insensitive (28 %). We observed similar test characteristics for a target Cmax target of 6.6 mg/L, and a target area under the drug concentration-versus-time curve (AUC0-8) target of 24.1 mg•hour/L. The urine colorimetric assay was specific but insensitive to detect low rifampin serum concentrations among HIV/TB patients. In future work we will attempt to optimize sampling times and assay performance, with the goal of delivering a method that can translate into a point-of-care assessment of rifampin exposure during anti-TB therapy.

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15 citations in Web of Science
13 citations in Scopus

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Collaboration types
Domestic collaboration
International collaboration
Web of Science research areas
Infectious Diseases
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