Effect of Dose Formulation on Isoniazid Absorption in Two Young Children

Abstract

In an 8-month-old infant with tuberculous meningitis treatment with isoniazid was unsuccessful and was associated with lower than expected plasma concentrations of isoniazid (measured concentration 0.1 µg/mL). The infant had received isoniazid as a crushed tablet admixed with apple sauce. Oral administration of the parenteral solution of isoniazid (Nydrazid, Squibb) mixed in apple juice produced a higher isoniazid concentration (2.9 µg/mL) and the child improved clinically. Pharmacokinetic studies in two subjects were performed following intramuscular injection of isoniazid and oral administration of (1) an isoniazid tablet crushed and mixed with apple sauce, (2) parenteral isoniazid solution mixed with apple juice, and (3) a commercially available syrup containing isoniazid and pyridoxine (P-I-N Forte, Lannett). Of the three oral preparations, the syrup produced the highest peak concentrations (8.3 and 6.9 µg/mL). The crushed tablet in apple sauce produced the lowest peak concentrations (1.4 and 2.4 µg/mL). Administration of crushed isoniazid tablets with food may be associated with impaired gastrointestinal absorption, lower than expected isoniazid concentrations, and treatment failure.