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Effect of dose formulation on isoniazid absorption in two young children
Pediatrics
|June 1, 1986
Summary
Crushing isoniazid tablets with food, like apple sauce, led to low drug levels and treatment failure in an infant. Using liquid isoniazid formulations significantly improved drug absorption and clinical outcomes.
Area of Science:
- Pharmacology
- Pediatrics
- Infectious Diseases
Background:
- Tuberculous meningitis requires effective antimicrobial therapy, with isoniazid being a key component.
- Suboptimal plasma concentrations of isoniazid can lead to treatment failure, particularly in infants.
- The formulation and administration method of oral isoniazid may significantly impact its bioavailability.
Purpose of the Study:
- To investigate the impact of different oral isoniazid formulations on plasma concentrations in an infant.
- To compare the pharmacokinetic profiles of crushed isoniazid tablets versus liquid formulations.
- To identify optimal administration strategies for isoniazid in pediatric patients.
Main Methods:
- Case study of an infant with tuberculous meningitis and treatment failure due to low isoniazid levels.
- Pharmacokinetic analysis comparing intramuscular injection with oral administration of crushed tablets in apple sauce, parenteral solution in apple juice, and a commercial syrup.
- Measurement of isoniazid plasma concentrations following different administration routes and formulations.
Main Results:
- An infant treated with crushed isoniazid tablets in apple sauce showed very low plasma concentrations (0.1 microgram/mL) and clinical deterioration.
- Oral administration of parenteral isoniazid solution in apple juice resulted in higher concentrations (2.9 micrograms/mL) and clinical improvement.
- Pharmacokinetic studies in two subjects revealed that the commercial syrup yielded the highest peak isoniazid concentrations (8.3 and 6.9 micrograms/mL), while crushed tablets in apple sauce yielded the lowest (1.4 and 2.4 micrograms/mL).
Conclusions:
- Administration of crushed isoniazid tablets mixed with food, such as apple sauce, may impair gastrointestinal absorption.
- This impaired absorption can lead to subtherapeutic isoniazid concentrations and potential treatment failure.
- Liquid formulations, particularly commercial syrups, appear to offer superior bioavailability for isoniazid in pediatric patients.
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