RT Journal Article
T1 Adequacy of the 10 mg/kg Daily Dose of Antituberculosis Drug Isoniazid in Infants under 6 Months of Age
A1 López Ramos, María Goretti
A1 Prieto Tato, Luis Manuel
A1 Ramos Amador, José Tomás
A1 Noguera Julian, Antoni
AB In 2010, the WHO recommended an increase in the daily doses of first-line anti-tuberculosis medicines in children. We aim to characterize the pharmacokinetics of the once-daily isoniazid (INH) dose at 10 mg/kg of body weight in infants <6 months of age. We performed a multicenter pharmacokinetic study in Spain. The N-acetyltransferase 2 gene was analyzed to determine the acetylation status. Samples were analyzed using a validated UPLC-UV assay. A non-compartmental pharmacokinetic analysis was performed. Twenty-three pharmacokinetic profiles were performed in 20 infants (8 females) at a median (IQR) age of 19.0 (12.6–23.3) weeks. The acetylator statuses were homozygous fast (n = 1), heterozygous intermediate (n = 12), and homozygous slow (n = 7). INH median (IQR) Cmax and AUC0–24h values were 4.8 (3.7–6.7) mg/L and 23.5 (13.4–36.7) h*mg/L and the adult targets (>3 mg/L and 11.6–26.3 h*mg/L) were not reached in three and five cases, respectively. The age at assessment or acetylator status had no impact on Cmax values, but a larger INH AUC0–24h (p = 0.025) and trends towards a longer half-life (p = 0.055) and slower clearance (p = 0.070) were observed in homozygous slow acetylators. Treatment was well tolerated; mildly elevated alanine aminotransferase levels were observed in three cases. In our series of young infants receiving isoniazid, no major safety concerns were raised, and the target adult levels were reached in most patients.
PB MDPI
YR 2023
FD 2023-01-30
LK https://hdl.handle.net/20.500.14352/110584
UL https://hdl.handle.net/20.500.14352/110584
LA eng
NO López-Ramos, M.G.; Vinent, J.; Aarnoutse, R.; Colbers, A.; Velasco-Arnaiz, E.; Martorell, L.; Falcón-Neyra, L.; Neth, O.; Prieto, L.; Guillén, S.; et al. Adequacy of the 10 mg/kg Daily Dose of Antituberculosis Drug Isoniazid in Infants under 6 Months of Age. Antibiotics 2023, 12, 272. https://doi.org/10.3390/antibiotics12020272
NO 2023 Descuento MDPI
NO Ministerio de Economía y Competitividad (España)
NO Instituto de Salud Carlos III
DS Docta Complutense
RD 20 abr 2025