Isoniazid urine spectrophotometry for prediction of serum pharmacokinetics in adults with TB
BACKGROUND: Isoniazid (INH) is an important drug in many TB regimens, and unfavorable treatment outcomes can be caused by suboptimal pharmacokinetics. Dose adjustment can be personalized by measuring peak serum concentrations; however, the process involves cold-chain preservation and laboratory tech...
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International Union Against Tuberculosis and Lung Disease (The Union)
2024-02-01
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| Series: | IJTLD Open |
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| Online Access: | https://www.ingentaconnect.com/contentone/iuatld/ijtldo/2024/00000001/00000002/art00006 |
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| author | P. S. Rao K. Reed N. Modi D. Handler K. Petros de Guex S. Yu L. Kagan R. Reiss N. Narayanan C. A. Peloquin A. Lardizabal C. Vinnard T. A. Thomas Y. L. Xie S. K. Heysell |
| author_facet | P. S. Rao K. Reed N. Modi D. Handler K. Petros de Guex S. Yu L. Kagan R. Reiss N. Narayanan C. A. Peloquin A. Lardizabal C. Vinnard T. A. Thomas Y. L. Xie S. K. Heysell |
| author_sort | P. S. Rao |
| collection | DOAJ |
| description | BACKGROUND: Isoniazid (INH) is an important drug in many TB regimens, and unfavorable treatment outcomes can be caused by suboptimal pharmacokinetics. Dose adjustment can be personalized by measuring peak serum concentrations; however, the process involves cold-chain preservation and laboratory techniques such as liquid chromatography (LC)/mass spectrometry (MS), which are unavailable in many high-burden settings. Urine spectrophotometry could provide a low-cost alternative with simple sampling and quantification methods. METHODS: We enrolled 56 adult patients on treatment for active TB. Serum was collected at 0, 1, 2, 4, 6, and 8 h for measurement of INH concentrations using validated LC-MS/MS methods. Urine was collected at 0–4, 4–8, and 8–24 h intervals, with INH concentrations measured using colorimetric methods. RESULTS: The median peak serum concentration and total serum exposure over 24 h were 4.8 mg/L and 16.4 mg*hour/L, respectively. Area under the receiver operator characteristic curves for urine values predicting a subtherapeutic serum concentration (peak <3.0 mg/L) were as follows: 0–4 h interval (AUC 0.85, 95% CI 0.7–0.96), 0–8 h interval (AUC 0.85, 95% CI 0.71–0.96), and 0–24 h urine collection interval (AUC 0.84, 95% CI 0.68–0.96). CONCLUSION: Urine spectrophotometry may improve feasibility of personalized dosing in high TB burden regions but requires further study of target attainment following dose adjustment based on a urine threshold. |
| format | Article |
| id | doaj-art-02f0e20885404c22a2a144e2b8ffa5d9 |
| institution | Kabale University |
| issn | 3005-7590 |
| language | English |
| publishDate | 2024-02-01 |
| publisher | International Union Against Tuberculosis and Lung Disease (The Union) |
| record_format | Article |
| series | IJTLD Open |
| spelling | doaj-art-02f0e20885404c22a2a144e2b8ffa5d92025-01-21T10:20:39ZengInternational Union Against Tuberculosis and Lung Disease (The Union)IJTLD Open3005-75902024-02-0112909510.5588/ijtldopen.23.03616Isoniazid urine spectrophotometry for prediction of serum pharmacokinetics in adults with TBP. S. Rao0K. Reed1N. Modi2D. Handler3K. Petros de Guex4S. Yu5L. Kagan6R. Reiss7N. Narayanan8C. A. Peloquin9A. Lardizabal10C. Vinnard11T. A. Thomas12Y. L. Xie13S. K. Heysell14Division of Infectious Diseases and International Health, andSchool of Arts and Sciences, University of Virginia, Charlottesville, VA,Public Health Research Institute and Global Tuberculosis Institute, Rutgers New Jersey Medical School, Newark, NJ,Public Health Research Institute and Global Tuberculosis Institute, Rutgers New Jersey Medical School, Newark, NJ,Division of Infectious Diseases and International Health, andDepartment of Pharmaceutics and Center of Excellence for Pharmaceutical Translational Research and Education, Ernest Mario School of Pharmacy, Rutgers State University of New Jersey, Newark, NJ,Department of Pharmaceutics and Center of Excellence for Pharmaceutical Translational Research and Education, Ernest Mario School of Pharmacy, Rutgers State University of New Jersey, Newark, NJ,Public Health Research Institute and Global Tuberculosis Institute, Rutgers New Jersey Medical School, Newark, NJ,Department of Pharmaceutics and Center of Excellence for Pharmaceutical Translational Research and Education, Ernest Mario School of Pharmacy, Rutgers State University of New Jersey, Newark, NJ,College of Pharmacy and Emerging Pathogens Institute, University of Florida, Gainesville, FL, USAPublic Health Research Institute and Global Tuberculosis Institute, Rutgers New Jersey Medical School, Newark, NJ,Public Health Research Institute and Global Tuberculosis Institute, Rutgers New Jersey Medical School, Newark, NJ,Division of Infectious Diseases and International Health, andPublic Health Research Institute and Global Tuberculosis Institute, Rutgers New Jersey Medical School, Newark, NJ,Division of Infectious Diseases and International Health, andBACKGROUND: Isoniazid (INH) is an important drug in many TB regimens, and unfavorable treatment outcomes can be caused by suboptimal pharmacokinetics. Dose adjustment can be personalized by measuring peak serum concentrations; however, the process involves cold-chain preservation and laboratory techniques such as liquid chromatography (LC)/mass spectrometry (MS), which are unavailable in many high-burden settings. Urine spectrophotometry could provide a low-cost alternative with simple sampling and quantification methods. METHODS: We enrolled 56 adult patients on treatment for active TB. Serum was collected at 0, 1, 2, 4, 6, and 8 h for measurement of INH concentrations using validated LC-MS/MS methods. Urine was collected at 0–4, 4–8, and 8–24 h intervals, with INH concentrations measured using colorimetric methods. RESULTS: The median peak serum concentration and total serum exposure over 24 h were 4.8 mg/L and 16.4 mg*hour/L, respectively. Area under the receiver operator characteristic curves for urine values predicting a subtherapeutic serum concentration (peak <3.0 mg/L) were as follows: 0–4 h interval (AUC 0.85, 95% CI 0.7–0.96), 0–8 h interval (AUC 0.85, 95% CI 0.71–0.96), and 0–24 h urine collection interval (AUC 0.84, 95% CI 0.68–0.96). CONCLUSION: Urine spectrophotometry may improve feasibility of personalized dosing in high TB burden regions but requires further study of target attainment following dose adjustment based on a urine threshold.https://www.ingentaconnect.com/contentone/iuatld/ijtldo/2024/00000001/00000002/art00006tuberculosisinhlc-ms/mspk |
| spellingShingle | P. S. Rao K. Reed N. Modi D. Handler K. Petros de Guex S. Yu L. Kagan R. Reiss N. Narayanan C. A. Peloquin A. Lardizabal C. Vinnard T. A. Thomas Y. L. Xie S. K. Heysell Isoniazid urine spectrophotometry for prediction of serum pharmacokinetics in adults with TB IJTLD Open tuberculosis inh lc-ms/ms pk |
| title | Isoniazid urine spectrophotometry for prediction of serum pharmacokinetics in adults with TB |
| title_full | Isoniazid urine spectrophotometry for prediction of serum pharmacokinetics in adults with TB |
| title_fullStr | Isoniazid urine spectrophotometry for prediction of serum pharmacokinetics in adults with TB |
| title_full_unstemmed | Isoniazid urine spectrophotometry for prediction of serum pharmacokinetics in adults with TB |
| title_short | Isoniazid urine spectrophotometry for prediction of serum pharmacokinetics in adults with TB |
| title_sort | isoniazid urine spectrophotometry for prediction of serum pharmacokinetics in adults with tb |
| topic | tuberculosis inh lc-ms/ms pk |
| url | https://www.ingentaconnect.com/contentone/iuatld/ijtldo/2024/00000001/00000002/art00006 |
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