Pharmacokinetics of isoniazid in children with tuberculosis—A comparative study at two doses
Aim To compare the pharmacokinetics of isoniazid (INH) at doses 5 and 10 mg/kg/day. Methods INH concentrations were estimated by high‐performance liquid chromatography in 24 Indian children aged 1 to 15 years on antituberculosis therapy. Blood samples were collected at 0, 2, 4, 6, 8 hours after admi...
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Published in | Pediatric pulmonology Vol. 55; no. 3; pp. 660 - 665 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Wiley Subscription Services, Inc
01.03.2020
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Subjects | |
Online Access | Get full text |
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Summary: | Aim
To compare the pharmacokinetics of isoniazid (INH) at doses 5 and 10 mg/kg/day.
Methods
INH concentrations were estimated by high‐performance liquid chromatography in 24 Indian children aged 1 to 15 years on antituberculosis therapy. Blood samples were collected at 0, 2, 4, 6, 8 hours after administration of INH. Patients were randomly given INH at 5 or 10 mg/kg/day and maximum concentrations (Cmax) and area under the curve (AUC(0‐8)) were determined in each group. The 2‐hour concentration of INH was used as Cmax for this study.
Results
Mean (standard deviation) Cmax was reached in 2 hours and was 2.68 ± 1.19 µg/mL in 5 mg/kg/day group and 8.86 ± 3.94 µg/mL in 10 mg/kg/day group (P < .05). The normal therapeutic range at 2‐hour concentrations for INH in adults achieving good clinical response is between 3 and 5 µg/mL. Among 5 mg/kg/day, only 4 (33%) patients had INH concentrations within the 2‐hour concentrations therapeutic range whereas in 10 mg/kg/day group, 11 (91%) patients achieved Cmax higher than the 2‐hour concentrations therapeutic range and 1 (9%) patient had Cmax within the 2‐hour concentrations therapeutic range. The mean AUC(0‐8) in 5 mg/kg/day group was 10.04 ± 6.12 and 35.93 ± 25.37 µg·h/mL in 10 mg/kg/day group (P = .0001).
Conclusion
Children on daily INH 10 mg/kg/day have higher AUC and Cmax than the required therapeutic range whereas over 65% of children with daily 5 mg/kg/day INH therapy failed to achieve the optimal therapeutic range. |
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ISSN: | 8755-6863 1099-0496 |
DOI: | 10.1002/ppul.24624 |