Pharmacokinetic Analysis of an Isoniazid Suspension Among Spanish Children Under 6 Years of Age
<b>Background</b>: Isoniazid (INH) remains a first-line drug for the treatment of tuberculosis (TB) in young children. In 2010, the WHO recommended an increase in the daily dose of INH up to 10 (7–15) mg/kg. Currently, there are no INH suspensions available in Europe. <b>Methods<...
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| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-01-01
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| Series: | Antibiotics |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2079-6382/14/1/74 |
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| Summary: | <b>Background</b>: Isoniazid (INH) remains a first-line drug for the treatment of tuberculosis (TB) in young children. In 2010, the WHO recommended an increase in the daily dose of INH up to 10 (7–15) mg/kg. Currently, there are no INH suspensions available in Europe. <b>Methods</b>: We aimed to characterize the pharmacokinetics of a licensed INH suspension (10 mg/mL, Pharmascience Inc., Montreal, QC, Canada) in children receiving INH daily at 10 mg/kg in a single-center, open-label, non-randomized, phase IIa clinical trial (EudraCT Number: 2016-002000-31) in Barcelona (Spain). Samples were analyzed using a validated UPLC-UV assay. The <i>N</i>-acetyltransferase 2 gene was examined to determine the acetylation status. A non-compartmental pharmacokinetic analysis was conducted. <b>Results</b>: Twenty-four patients (12 females) were included (primary chemoprophylaxis, <i>n</i> = 12; TB treatment, <i>n</i> = 9; and TB infection preventive treatment, <i>n</i> = 3). The acetylator statuses were homozygous fast (<i>n</i> = 3), heterozygous intermediate (<i>n</i> = 18), and homozygous slow (<i>n</i> = 2; unavailable in one patient). The INH median (IQR) C<sub>max</sub> and AUC<sub>0–24h</sub> values were 6.1 (4.5–8.2) mg/L and 23.0 (11.2–35.4) h∙mg/L; adult targets (>3 mg/L and 11.6–26.3 h∙mg/L) were not achieved in three and six cases, respectively. Gender, age at assessment (<2 or >2 years), and INH monotherapy (vs. combined TB treatment) had no impact on pharmacokinetic parameters. Significant differences in C<sub>max</sub> (<i>p</i> = 0.030) and AUC<sub>0–24h</sub> (<i>p</i> = 0.011) values were observed based on acetylator status. Treatment was well tolerated, and no severe adverse events were observed; three patients developed asymptomatic mildly elevated alanine aminotransferase levels. <b>Conclusions</b>: In infants and children receiving a daily INH suspension at 10 mg/kg, no safety concerns were raised, and the target adult levels were reached in the majority of patients. |
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| ISSN: | 2079-6382 |