Isoniazid acetylation metabolic ratio during maturation in children

Isoniazid acetylation metabolic ratio (MR) was studied in 61 children with tuberculosis after administration of isoniazid. MR was calculated as the molar acetylisoniazid to isoniazid concentration ratio. MR was used as a probe for N‐acetyltransferase activity and to determine the acetylation phenoty...

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Bibliographic Details
Published in:Clinical pharmacology and therapeutics 1997-10, Vol.62 (4), p.377-383
Main Authors: Pariente‐Khayat, Ann, Rey, Elisabeth, Gendrel, Dominique, Vauzelle‐Kervroëdan, Françoise, Crémier, Odile, d'Athis, Philippe, Badoual, Jean, Olive, Georges, Pons, Gérard
Format: Article
Language:English
Subjects:
Acetylation
Adolescent
Aging - metabolism
Antibacterial agents
Antibiotics. Antiinfectious agents. Antiparasitic agents
Antitubercular Agents - pharmacokinetics
Arylamine N-Acetyltransferase - genetics
Arylamine N-Acetyltransferase - metabolism
Biological and medical sciences
Child
Child, Preschool
Humans
Infant
Infant, Newborn
Isoniazid - pharmacokinetics
Medical sciences
Pharmacology. Drug treatments
Phenotype
Retrospective Studies
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Summary:Isoniazid acetylation metabolic ratio (MR) was studied in 61 children with tuberculosis after administration of isoniazid. MR was calculated as the molar acetylisoniazid to isoniazid concentration ratio. MR was used as a probe for N‐acetyltransferase activity and to determine the acetylation phenotype. MR had a bimodal distribution with an antimode between 0.48 and 0.77. MR and the percentage of fast acetylators increased significantly with age. The cumulative frequency of fast acetylators increased with age, with a plateau reached around 4 years. MR value was checked during treatment in 44 children. All children but one who initially appeared as fast acetylators remained in this group after repeated testing. Among the 30 slow acetylators, 12 became fast acetylators, and 10 showed a variable phenotyping at different ages. A bimodal distribution of the isoniazid acetylation MR was shown in children, with an antimode close to that described in the literature and a maturation of isoniazid acetylation during the first 4 years. Clinical Pharmacology & Therapeutics (1997) 62, 377–383; doi:
ISSN:0009-9236
1532-6535
DOI:10.1016/S0009-9236(97)90115-6