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

BACKGROUND: 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 a...

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Autores principales: Zentner, Isaac, Schlecht, Hans P., Khensouvann, Lorna, Tamuhla, Neo, Kutzler, Michele, Ivaturi, Vijay, Pasipanodya, Jotam G., Gumbo, Tawanda, Peloquin, Charles A., Bisson, Gregory P., Vinnard, Christopher
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4888587/
https://www.ncbi.nlm.nih.gov/pubmed/27250739
http://dx.doi.org/10.1186/s12879-016-1576-1
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author Zentner, Isaac
Schlecht, Hans P.
Khensouvann, Lorna
Tamuhla, Neo
Kutzler, Michele
Ivaturi, Vijay
Pasipanodya, Jotam G.
Gumbo, Tawanda
Peloquin, Charles A.
Bisson, Gregory P.
Vinnard, Christopher
author_facet Zentner, Isaac
Schlecht, Hans P.
Khensouvann, Lorna
Tamuhla, Neo
Kutzler, Michele
Ivaturi, Vijay
Pasipanodya, Jotam G.
Gumbo, Tawanda
Peloquin, Charles A.
Bisson, Gregory P.
Vinnard, Christopher
author_sort Zentner, Isaac
collection PubMed
description BACKGROUND: 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. METHODS: 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. RESULTS: 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 (C(max)) 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 C(max) target of 6.6 mg/L, and a target area under the drug concentration-versus-time curve (AUC(0–8)) target of 24.1 mg•hour/L. CONCLUSIONS: 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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spelling pubmed-48885872016-06-08 Urine colorimetry to detect Low rifampin exposure during tuberculosis therapy: a proof-of-concept study Zentner, Isaac Schlecht, Hans P. Khensouvann, Lorna Tamuhla, Neo Kutzler, Michele Ivaturi, Vijay Pasipanodya, Jotam G. Gumbo, Tawanda Peloquin, Charles A. Bisson, Gregory P. Vinnard, Christopher BMC Infect Dis Research Article BACKGROUND: 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. METHODS: 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. RESULTS: 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 (C(max)) 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 C(max) target of 6.6 mg/L, and a target area under the drug concentration-versus-time curve (AUC(0–8)) target of 24.1 mg•hour/L. CONCLUSIONS: 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. BioMed Central 2016-06-01 /pmc/articles/PMC4888587/ /pubmed/27250739 http://dx.doi.org/10.1186/s12879-016-1576-1 Text en © The Author(s). 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Zentner, Isaac
Schlecht, Hans P.
Khensouvann, Lorna
Tamuhla, Neo
Kutzler, Michele
Ivaturi, Vijay
Pasipanodya, Jotam G.
Gumbo, Tawanda
Peloquin, Charles A.
Bisson, Gregory P.
Vinnard, Christopher
Urine colorimetry to detect Low rifampin exposure during tuberculosis therapy: a proof-of-concept study
title Urine colorimetry to detect Low rifampin exposure during tuberculosis therapy: a proof-of-concept study
title_full Urine colorimetry to detect Low rifampin exposure during tuberculosis therapy: a proof-of-concept study
title_fullStr Urine colorimetry to detect Low rifampin exposure during tuberculosis therapy: a proof-of-concept study
title_full_unstemmed Urine colorimetry to detect Low rifampin exposure during tuberculosis therapy: a proof-of-concept study
title_short Urine colorimetry to detect Low rifampin exposure during tuberculosis therapy: a proof-of-concept study
title_sort urine colorimetry to detect low rifampin exposure during tuberculosis therapy: a proof-of-concept study
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4888587/
https://www.ncbi.nlm.nih.gov/pubmed/27250739
http://dx.doi.org/10.1186/s12879-016-1576-1
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