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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| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
International Union Against Tuberculosis and Lung Disease (The Union)
2024-02-01
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| Series: | IJTLD Open |
| Subjects: | |
| Online Access: | https://www.ingentaconnect.com/contentone/iuatld/ijtldo/2024/00000001/00000002/art00006 |
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| Summary: | 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. |
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| ISSN: | 3005-7590 |