| ORIGINAL ARTICLE |
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| Year : 2020 | Volume
: 9
| Issue : 4 | Page : 411-416 |
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Urine colorimetry for levofloxacin pharmacokinetics and personalized dosing in people with drug-resistant tuberculosis
Prakruti Rao1, Svetlana Zhdanova2, Oleg Ogarkov3, Elizaveta Orlova4, Andrew Ebers5, Suzanne Stroup1, Shino Mirawdaly1, Daniel Van Aartsen1, Olga Koshkina4, Alexey Suzdalnitsky4, Elena Moiseeva4, Rebecca Dillingham1, Scott K Heysell1
1 Division of Infectious Diseases and International Health, University of Virginia, Charlottesville, Virginia, USA
2 Department of Epidemiology and Microbiology, Scientific Center for Family Health and Human Reproduction Problems, Irkutsk, Russia
3 Department of Epidemiology and Microbiology, Scientific Center for Family Health and Human Reproduction Problems; Department of Medicine, Irkutsk State Medical Academy of Continuing Education, Irkutsk, Russia
4 Department of Medicine, Irkutsk Regional Tuberculosis Referral Hospital, Irkutsk, Russia
5 Department of Medicine, University of Arkansas for Medical Sciences, Fayetteville, AR, USA
Correspondence Address:
Scott K Heysell
345 Crispell Dr., MR-6 Building, University of Virginia, Charlottesville 22908, Virginia
USA
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/ijmy.ijmy_186_20
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Background: Levofloxacin is a preferred drug for multidrug-resistant (MDR)-tuberculosis (TB) with bactericidal activity that correlates with the pharmacokinetic exposures of serum peak concentration (Cmax) and total area under the concentration time curve (AUC0-24). Pharmacokinetic exposures can be measured to personalize dosing to reach targets, but this practice requires venepuncture, chromatographic or mass spectrometry equipment, and technical expertise. We sought to demonstrate the accuracy of using urine colorimetry as a more feasible estimation of levofloxacin exposure. Method: A colorimetric method using bromocresol green was tested on spiked urine samples with levofloxacin measured using a spectrophotometer. This method was tested in urine samples of healthy volunteers given one 750 mg dose of levofloxacin with urine collected at 0–4 h, 4–8 h, and 8–24 h intervals, and concomitant serum samples were collected and analyzed by high-performance liquid chromatography. Validation of this assay was done in a cohort of people living with human immunodeficiency virus (PLWH), initiating a levofloxacin containing MDR-TB regimen. Results: Urine colorimetry was reproducible in spiked samples and the calibration was curve linear for levofloxacin concentrations ranging from 7.8 μg/ml to 250 μg/ml, with r = 0.98. In healthy volunteers, correlation between urine absorbance values and serum AUC0-24 was highest in urine collected between 4 and 8 h (r = 0.91, P = 0.01), yet in PLWH, urine collected between 0 and 4 h had highest correlation (r = 0.66, P = 0.05). The area under the receiver operating characteristics curve was >0.8 in the derivation, as well as the validation cohort for the urine absorbance values identifying people with total serum exposure below target. Conclusion: Urine colorimetry was highly sensitive in predicting target serum concentrations. Colorimetric methods to determine levofloxacin in urine may improve the feasibility of therapeutic drug monitoring and personalized dose adjustment in TB endemic settings.
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