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[The pharmacokinetics of isoniazid in children (author's transl)]
Insights
Children metabolize isoniazid (INH) faster than adults, requiring higher, individualized doses. This study analyzed INH metabolism in pediatric patients to inform optimal dosing strategies.
Area of Science:
- Pharmacokinetics
- Pediatric Pharmacology
- Drug Metabolism
Context:
- Isoniazid (INH) is a primary treatment for tuberculosis.
- Understanding pediatric drug metabolism is crucial for effective treatment.
- Previous studies have not fully elucidated INH pharmacokinetics in children.
Purpose:
- To investigate isoniazid (INH) metabolism in children aged 0.5 to 17 years.
- To establish guidelines for appropriate INH pediatric dosing.
- To compare INH metabolic parameters between children and adults.
Summary:
- Children exhibit similar acetylator phenotypes (slow vs. fast) as adults.
- Pediatric patients show lower INH inactivation indices but higher distribution volumes and plasma clearances compared to adults.
- Plasma half-lives of INH are comparable between pediatric and adult populations.
Impact:
- Children metabolize INH more rapidly, likely due to a higher liver weight to body weight ratio and increased first-pass effect.
- Recommended INH doses in children should be higher than in adults.
- Individualized dosing is essential for optimizing INH therapy in pediatric patients.
Abstract:
The purpose of this study, which involved 134 children aged between 0.5 and 17 years, was to investigate the metabolism of isoniazid (INH) in children and to provide guide-lines for dosage. The distribution of slow (55,5%) and fast (44,5%) acetylators was the same in children as in adults. However, the mean of INH inactivation index were lower (0.23 and 0.48) while distribution volumes, (1.30 +/- 0.06 and 1.57 +/- 0.17 1/kg) and total plasma clearances (5.39 +/- 0.43 and 14.7 +/- 1.5 ml/Kg/min) were higher than in adults. Plasma half-lives were similar in children and adults. These results indicate that INH is more rapidly metabolized in children owing, it is suggested to a higher liver weight : body weight ratio and to a more pronounced first pass effect. The doses of INH therefore must be higher in children and strictly adapted to each individual.