title: Urine colorimetry to detect Low rifampin exposure during tuberculosis therapy: a proof-of-concept study.
abstract: 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.
authors.affiliation: Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, Philadelphia, PA, USA.
authors.forename: Isaac
authors.initials: I
authors.lastname: Zentner
authors.affiliation: Department of Medicine, Division of Infectious Diseases, Drexel University College of Medicine, Philadelphia, PA, USA.
authors.forename: Hans P
authors.initials: HP
authors.lastname: Schlecht
authors.affiliation: Genomind, Inc, King of Prussia, PA, USA.
authors.forename: Lorna
authors.initials: L
authors.lastname: Khensouvann
authors.affiliation: Botswana-Upenn Partnership, Gaborone, Botswana.
authors.forename: Neo
authors.initials: N
authors.lastname: Tamuhla
authors.affiliation: Department of Medicine, Division of Infectious Diseases, Drexel University College of Medicine, Philadelphia, PA, USA.
authors.forename: Michele
authors.initials: M
authors.lastname: Kutzler
authors.affiliation: Center for Translational Medicine, School of Pharmacy, University of Maryland, Baltimore, MD, USA.
authors.forename: Vijay
authors.initials: V
authors.lastname: Ivaturi
authors.affiliation: Center for Infectious Disease Research and Experimental Therapeutics, Baylor Research Institute, Baylor University Medical Center, Dallas, TX, USA.
authors.forename: Jotam G
authors.initials: JG
authors.lastname: Pasipanodya
authors.affiliation: Center for Infectious Disease Research and Experimental Therapeutics, Baylor Research Institute, Baylor University Medical Center, Dallas, TX, USA.
authors.forename: Tawanda
authors.initials: T
authors.lastname: Gumbo
authors.affiliation: College of Pharmacy and Emerging Pathogens Institute, University of Florida, Gainesville, FL, USA.
authors.forename: Charles A
authors.initials: CA
authors.lastname: Peloquin
authors.affiliation: Department of Medicine, Division of Infectious Disease, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Gregory P
authors.initials: GP
authors.lastname: Bisson
authors.affiliation: Public Health Research Institute, New Jersey Medical School, Rutgers University, Newark, USA. christopher.vinnard@rutgers.edu.
authors.forename: Christopher
authors.initials: C
authors.lastname: Vinnard
mesh_terms: D000328:Adult; D000995:Antitubercular Agents / Q000032:analysis / Q000627:therapeutic use* / Q000652:urine*; D001902:Botswana; D003124:Colorimetry / Q000379:methods; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring / Q000379:methods*; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D012372:ROC Curve; D012293:Rifampin / Q000032:analysis / Q000627:therapeutic use* / Q000652:urine*; D012680:Sensitivity and Specificity; D013048:Specimen Handling; D014376:Tuberculosis / Q000188:drug therapy* / Q000652:urine; D016482:Urinalysis / Q000379:methods*
chemical_list: D000995:Antitubercular Agents; D012293:Rifampin
keywords: Point-of-care; Therapeutic drug monitoring; Tuberculosis