Pharmacokinetics and Drug Disposition

Clinical Pharmacology & Therapeutics (1997) 62, 377–383; doi:

Isoniazid acetylation metabolic ratio during maturation in children

Ann Pariente-Khayat MD1, Elisabeth Rey PharmD1, Dominique Gendrel MD, PhD1, Françoise Vauzelle-Kervroëdan MD1, Odile Crémier MD1, Philippe d'Athis PhD1, Jean Badoual MD1, Georges Olive MD1 and Gérard Pons MD, PhD1

1Pharmacologie Périnatale et Pédiatrique, Université René Descartes Paris V, Hôpital Saint-Vincent de Paul (Assistance Publique-Hôpitaux de Paris), and Pédiatrie B, Hôpital Saint-Vincent de Paul (Assistance Publique-Hôpitaux de Paris), Paris, France.

Correspondence: Gérard Pons, MD, PhD, Pharmacologie Périnatale et Pédiatrique, Hôpital Saint-Vincent de Paul, 82 avenue Denfert Rochereau, 75674 Paris Cédex 14, France.

Received 30 December 1996; Accepted 23 June 1997.

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Abstract

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.

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