The pharmacogenetics of NAT2 enzyme maturation in perinatally HIV exposed infants receiving isoniazid

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dc.contributor.authorZhu R.
dc.contributor.authorKiser J.J.
dc.contributor.authorSeifart H.I.
dc.contributor.authorWerely C.J.
dc.contributor.authorMitchell C.D.
dc.contributor.authorD'Argenio D.Z.
dc.contributor.authorFletcher C.V.
dc.date.accessioned2012-04-20T07:09:22Z
dc.date.available2012-04-20T07:09:22Z
dc.date.issued2012
dc.description.abstractThe roles of the NAT2 genotype and enzyme maturation on isoniazid pharmacokinetics were investigated in South African infants with perinatal HIV exposure enrolled in a randomized, double-blind, controlled trial of isoniazid for prevention of tuberculosis disease and latent infection. Plasma concentration-time measurements of isoniazid from 151 infants (starting at 3-4 months of age) receiving isoniazid 10 to 20 mg/kg/d orally during the course of the 24-month study were incorporated in a population analysis along with NAT2 genotype, body weight, age, and sex. The results showed a different NAT2 enzyme maturation profile for each of the 3 acetylation groups, with the 70-kg body weight-normalized typical apparent clearance for the fast and intermediate acetylators increasing from 14.25 L/h and 10.88 L/h at 3 months of age to 22.84 L/h and 15.58 L/h at 24 months of age, respectively, with no significant change in the apparent clearance of the slow group during this period. A hypothesis is proposed to explain the genotype-dependent enzyme maturation processes for the NAT2 enzyme. © 2012 The Author(s).
dc.identifier.citationJournal of Clinical Pharmacology
dc.identifier.citation52
dc.identifier.citation4
dc.identifier.citation511
dc.identifier.citation519
dc.identifier.issn912700
dc.identifier.other10.1177/0091270011402826
dc.identifier.urihttp://hdl.handle.net/10019.1/20791
dc.subjectenzyme maturation
dc.subjectgenetic polymorphism
dc.subjectInfants
dc.subjectpharmacogenetics
dc.subjectpopulation pharmacokinetics
dc.titleThe pharmacogenetics of NAT2 enzyme maturation in perinatally HIV exposed infants receiving isoniazid
dc.typeArticle
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