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Rifampin urinary excretion to predict serum targets in children with tuberculosis: a prospective diagnostic accuracy study


Objective Pharmacokinetic variability drives tuberculosis (TB) treatment outcomes but measurement of serum drug concentrations for personalised dosing is inaccessible for children in TB-endemic settings. We compared rifampin urine excretion for prediction of a serum target associated with treatment outcome.

Design Prospective diagnostic accuracy study.

Setting Inpatient wards and outpatient clinics, northern Tanzania.

Patients Children aged 4–17 years were consecutively recruited on initiation of WHO-approved treatment regimens.

Interventions Samples were collected after directly observed therapy at least 2 weeks after initiation in the intensive phase: serum at pre-dose and 1, 2 and 6 hours post-dose, later analysed by liquid chromatography-tandem mass spectrometry for calculation of rifampin total exposure or area under the concentration time curve (AUC0-24); urine at post-dose intervals of 0–4, 4–8 and 8–24 hours, with rifampin excretion amount measured onsite by spectrophotometry.

Main outcome measures Receiver operating characteristic (ROC) curve for percentage of rifampin dose excreted in urine measured by spectrophotometry to predict serum rifampin AUC0–24 target of 31.7 mg*hour/L.

Results 89 children, 52 (58%) female, with median age of 9.1 years, had both serum and urine collection. Only 59 (66%) reached the serum AUC0–24 target, reflected by a range of urine excretion patterns. Area under the ROC curve for percentage of rifampin dose excreted in urine over 24 hours predicting serum AUC0–24 target was 69.3% (95% CI 56.7% to 81.8%), p=0.007.

Conclusions Urine spectrophotometry correlated with a clinically relevant serum target for rifampin, representing a step toward personalised dosing for children in TB-endemic settings.

  • Child Health
  • Communicable Diseases
  • Global Health
  • Infectious Disease Medicine
  • Paediatrics

Data availability statement

Data are available upon reasonable request. Data not included in supplementary material and standard operating procedures are available on request to the corresponding author.

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