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.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/S0009-9236(97)90115-6 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Pharmacokinetic Analysis of an Isoniazid Suspension Among Spanish Children Under 6 Years of Age.
Antibiotics (Basel)
January 2025
Malalties Infeccioses i Resposta Inflamatòria Sistèmica en Pediatria, Servei d'Infectologia, Institut de Recerca Pediàtrica Sant Joan de Déu, 08950 Barcelona, Spain.
: Isoniazid (INH) remains a first-line drug for the treatment of tuberculosis (TB) in young children. In 2010, the WHO recommended an increase in the daily dose of INH up to 10 (7-15) mg/kg. Currently, there are no INH suspensions available in Europe.
View Article and Find Full Text PDFThe Development of an Age-Appropriate Fixed Dose Combination for Tuberculosis Using Physiologically-Based Pharmacokinetic Modeling (PBBM) and Risk Assessment.
Pharmaceutics
December 2024
Simulations Plus, Inc., 42505 10th Street West, Lancaster, CA 93534-7059, USA.
The combination of isoniazid (INH) and rifampicin (RIF) is indicated for the treatment maintenance phase of tuberculosis (TB) in adults and children. In Brazil, there is no current reference listed drug for this indication in children. Farmanguinhos has undertaken the development of an age-appropriate dispersible tablet to be taken with water for all age groups from birth to adolescence.
View Article and Find Full Text PDF[Guidelines for diagnosis and management of drug-induced liver injury caused by anti-tuberculosis drugs (2024 version)].
Zhonghua Jie He He Hu Xi Za Zhi
November 2024
Article Synopsis
- Drug-induced liver injury (DILI), specifically anti-tuberculosis drug-induced liver injury (ATB-DILI), is a common side effect of tuberculosis treatment, prompting the Chinese Medical Association Tuberculosis Branch to create guidelines for better diagnosis and management.
- These guidelines cover various topics, including risk factors (such as genetic variations and existing liver conditions), clinical classification, and comprehensive diagnostic procedures like blood tests and imaging.
- Key recommendations include assessing liver function through specific biochemical tests, collecting detailed medical histories, and using liver biopsies for accurate diagnosis and prognosis of ATB-DILI.
Isoniazid-historical development, metabolism associated toxicity and a perspective on its pharmacological improvement.
Front Pharmacol
September 2024
Centre for Drug Discovery, BRIC-Translational Health Science and Technology Institute, Faridabad, Haryana, India.
Article Synopsis
- Isoniazid (INH) is an effective anti-tubercular drug, but its use is limited by serious side effects like liver damage and peripheral neuropathy due to its metabolism.
- The liver enzyme NAT-2 interacts with INH's terminal -NH group, potentially leading to toxic byproducts and deficiencies in essential nutrients like vitamin B6, which are linked to nerve damage.
- The review discusses INH's history, action mechanisms, clinical trial findings on side effects, and suggests developing modified chemical derivatives to minimize harmful metabolic effects.
Differential distribution of NAT2 polymorphisms and NAT2 acetylator phenotypes among indigenous populations of the Brazilian Amazon.
Pharmacogenet Genomics
December 2024
Departamento de Pesquisa, Divisão de Pesquisa Clínica e Desenvolvimento Tecnológico, Coordenação de Pesquisa, Instituto Nacional de Câncer, Rio de Janeiro, Brazil.
Objectives: We report, for the first time, the distribution of four no-function NAT2 single nucleotide polymorphisms and inferred NAT2 acetylator phenotypes in three indigenous groups (Munduruku, Paiter-Suruí, and Yanomami), living in reservation areas in the Brazilian Amazon.
Methods: Two hundred and seventy-six participants from three indigenous groups (92 for each group) were included and genotyped for four NAT2 polymorphisms (rs1801279, rs1801280, rs1799930, and rs1799931) by the TaqMan system. Minor Allele Frequency (MAF) was determined and NAT2 acetylator phenotypes were inferred.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!