Isoniazid Plasma Concentrations in a Cohort of South African Children with Tuberculosis: Implications for International Pediatric Dosing Guidelines

• DOI: 10.1086/598192
• Publication Date: 2009-04-24T21:54:20Z
• Authors: Helen McIlleron; Marianne Willemse; Cedric J. Werely; Gregory D. Hussey; H. Simon Schaaf; Peter J. Smith; Peter R. Donald
• Keywords: Dose; Interquartile range; Rifapentine

In most countries with a high burden of tuberculosis, children tuberculosis are prescribed isoniazid at dosages 4-6 mg/kg/day, as recommended by international authorities.We studied concentrations in 56 hospitalized (median age, 3.22 years; interquartile range [IQR], 1.58-5.38 years) who received daily dosage, 5.01 mg/kg/day; range, 2.94-15.58 mg/kg/day) part antituberculosis treatment. At 1 and 4 months after initiation treatment, were measured plasma samples 0.75, 1.5, 3, 4, 6 h treatment dose, to describe pharmacokinetic measures using noncompartmental analysis. The effects dose milogram per kilogram, acetylator genotype, sex, clinical diagnosis kwashiorkor human immunodeficiency virus (HIV) infection on evaluated.Median peak mg/kg 58% lower than those 8-10 (2.39 mg/L [IQR, 1.59-3.40] vs. 5.71 4.74-7.62]). Peak <3 70% mg/kg. contrast, 8-12 achieved approximating adults treated 300 mg daily. Intermediate or fast genotype independently predicted 38% (95% confidence interval [CI], 21%-51%) reduction concentrations, compared the slow-acetylator genotype. Each 1-mg/kg increase each year age associated increases 21% CI, 16%-25%) 6% 3%-10%), respectively.Younger require higher doses kilogram body weight achieve similar adults. A should be recommended.