Isoniazid pharmacokinetics in children according to acetylator phenotype.
The pharmacokinetics of isoniazid (INH) was studied in children (0-196 months old) according to their acetylator phenotype, estimated from the metabolic acetyl INH/INH molar plasma concentration ratio (MR) measured 3 h after INH oral administration. There were 17 slow (MR < 0.48) and 17 fast acetylators (MR > or = 0.48). The mean apparent plasma clearance was significantly lower, the mean apparent volume of distribution higher and the half-life longer in the slow acetylator group (C1, 0.298 +/- 0.099 L/h/kg; Vd, 1.56 +/- 0.65 L/kg; t1/2, 3.88 +/- 01.89 h) than in the fast acetylator group (Cl, 0.528 +/- 0.234 L/h/kg; Vd, 1.06 +/- 0.45; t1/2, 1.64 +/- 1.1 h). The half-life decreased with age. An impaired isoniazid elimination was suggested in children less than three months old, which may be in favour of an individual dose adjustment in this population.
Rey
E
E
Pharmacologie Périnatale et Pédiatrique, Hôpital St Vincent de Paul, Université René Descartes Paris V, France. elisabeth.rey@svp.ap-hop-paris.fr
Gendrel
D
D
Treluyer
J M
JM
Tran
A
A
Pariente-Khayat
A
A
d'Athis
P
P
Pons
G
G
D000107:Acetylation; D000293:Adolescent; D000367:Age Factors; D002648:Child; D002675:Child, Preschool; D006207:Half-Life; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007538:Isoniazid / Q000097:blood / Q000493:pharmacokinetics*; D008657:Metabolic Clearance Rate; D010641:Phenotype
D007538:Isoniazid