Urine colorimetry for levofloxacin pharmacokinetics and personalized dosing in people with drug-resistant tuberculosis
| Autor: | Elizaveta Orlova, Rebecca Dillingham, Elena P. Moiseeva, Daniel Van Aartsen, Alexey Suzdalnitsky, Svetlana Zhdanova, Shino Mirawdaly, Andrew Ebers, Scott K. Heysell, Oleg Ogarkov, Olga Koshkina, Suzanne Stroup, Prakruti Rao |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Microbiology (medical) therapeutic drug monitoring 030106 microbiology lcsh:QR1-502 Antitubercular Agents Cmax Urine lcsh:Microbiology Article Colorimetry (chemical method) 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Pharmacokinetics Levofloxacin Tuberculosis Multidrug-Resistant medicine Humans 030212 general & internal medicine Dosing people living with human immunodeficiency virus levofloxacin Chromatography Bromocresol green medicine.diagnostic_test business.industry multidrug-resistant tuberculosis Infectious Diseases ROC Curve chemistry Therapeutic drug monitoring Colorimetry Female Drug Monitoring business pharmacokinetics medicine.drug |
| Zdroj: | International journal of mycobacteriology International Journal of Mycobacteriology, Vol 9, Iss 4, Pp 411-416 (2020) |
| ISSN: | 2212-5531 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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