Pharmacokinetics of high-dose isoniazid in children affected by multidrug-resistant TB
| Autor: | Anthony J. Garcia-Prats, Anneke C. Hesseling, Jana Winckler, L E van der Laan, Helen McIlleron, Heather Draper, Lubbe Wiesner, Jennifer Norman, H S Schaaf, Peter R. Donald |
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| Rok vydání: | 2021 |
| Předmět: |
Pulmonary and Respiratory Medicine
Adult medicine.medical_specialty business.industry Isoniazid Cmax Area under the curve Antitubercular Agents Gastroenterology Article Geometric mean ratio Preventive therapy Infectious Diseases Pharmacokinetics Internal medicine Child Preschool Tuberculosis Multidrug-Resistant Multidrug-Resistant TB Medicine Humans business Child medicine.drug |
| Zdroj: | Int J Tuberc Lung Dis |
| ISSN: | 1815-7920 |
| Popis: | BACKGROUND: High-dose isoniazid (INHH) (15–20 mg/kg/day) could be administered to overcome low-level INH resistance, but pharmacokinetic data are sparse.METHODS: This observational study included South African children (H as preventive therapy, or treatment for multidrug-resistant TB (MDR-TB) exposure or disease. Pharmacokinetic sampling was performed after an INH dose of 20 mg/kg. Non-compartmental analysis and multivariable regression models were used to evaluate associations of key covariates with area under the curve (AUC0–24) and maximum concentration (Cmax). AUC and Cmax values were compared against proposed adult targets.RESULTS: Seventy-seven children were included, with median age of 3.7 years; 51 (66%) had MDR-TB disease and 26 (34%) had MDR-TB exposure. Five were HIV-positive, of whom four were ≥5 years old. The median AUC0–24 was 19.46 µgh/mL (IQR 10.76–50.06) and Cmax was 5.14 µg/mL (IQR 2.69–13.2). In multivariable analysis of children aged 0–24 (geometric mean ratio GMR 0.19, 95% CI 0.15–0.26; P < 0.001) and Cmax (GMR 0.20, 95% CI 0.15–0.26; P < 0.001).CONCLUSIONS: INH concentrations in children with MDR-TB disease were much lower than expected, but comparable to previous reports in children with MDR-TB exposure. Further studies should confirm these findings and explore possible causes. |
| Databáze: | OpenAIRE |
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