| Summary: | 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 (<i>n</i> = 1), heterozygous intermediate (<i>n</i> = 12), and homozygous slow (<i>n</i> = 7). INH median (IQR) C<sub>max</sub> and AUC<sub>0–24h</sub> 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 C<sub>max</sub> values, but a larger INH AUC<sub>0–24h</sub> (<i>p</i> = 0.025) and trends towards a longer half-life (<i>p</i> = 0.055) and slower clearance (<i>p</i> = 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.
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