Clinical Pharmacology of Isoniazid in Infants and Children
Author(s): Gian Maria Pacifici
Isoniazid (isonicotinic acid hydrazide), is used, with pyrazinamide or rifampin, in the primary treatment and re-treatment of tuberculosis. Tuberculosis is still the most important infectious killer of humans. Isoniazid is bacteriastatic, and at high concentrations, is bactericidal against Mycobacterium tuberculosis. This antibiotic enters bacilli by passive diffusion, and is activated to its toxic form with the bacillus by KatG, multifunctional catalyses-peroxidise. Isoniazid is metabolized to acetylisoniazid by N-acetylteansferase-2, which is polymorphic. Acetylisoniazid formation rate is higher in faster than slower acetylators. Thus, isoniazid plasma concentration is lower in faster than slower acetylators, and this has therapeutic implications: isoniazid half-life is shorter in faster than slower acetylators. Isoniazid doses are 5 mg/ kg, for the treatment of neonatal prophylaxis, 10 mg/kg for the treatment of neonatal latent tuberculosis infection, and 10 to 20 mg/kg in children. Isoniazid half-lives are 2 to 5 hours in infants and 1.5 to 2.5 hours in children. This antibiotic is safe in children; however increase of hepatic transaminase activities and excretion of vitamin B6 has been reported. Isoniazid migration into the breast-milk is poor and isoniazid concentration is not enough for tuberculosis prevention and prophylaxis. Infants, which are tuberculous-infected, should require appropriate antituberculosis chemotherapy. Isoniazid penetration into the cerebrospinal fluid is poor; however, isoniazid concentration is well above the MIC for Mycobacterium tuberculosis. Concomitant administration of isoniazid and rifampin induces hepatotoxicity in children. Isoniazid pharmacokinetics have been extensively studied in infants and children. Several bacteria may become resistant to isoniazid and, the consequent isoniazid-resistance is an obstacle to treatment of tuberculosis. The aim of this study is to review the published data of isoniazid effects, metabolism, pharmacokinetics, and bacteria-resistance in infants and children.
Will be updated soon