Premium
Population pharmacokinetic model of omeprazole following single oral doses in pediatric subjects
Author(s) -
Li J.,
Robbie G. J.,
Puchalski T.,
Winter H.,
Tzeng T.,
Birmingham B.,
Zhao J.,
Andersson T.,
Martin P.,
Lundborg P.
Publication year - 2004
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/j.clpt.2003.11.154
Subject(s) - pharmacokinetics , volume of distribution , oral administration , population , metabolic clearance rate , disposition , body weight , absorption (acoustics) , omeprazole , distribution (mathematics) , medicine , pharmacology , mathematics , psychology , social psychology , mathematical analysis , physics , acoustics , environmental health
Purpose To examine the effect of developmental changes on omeprazole (OME) pharmacokinetics (PK) in pediatric subjects. Methods OME plasma concentration time courses following single oral doses of 0.5–1.5 mg/kg, 10 and 20 mg in 84 pediatric subjects aged from 15 days to 16 years old were fitted to a one‐compartment disposition model with zero, first, simultaneous zero/first, and sequential zero/first order absorption models. An allometry model was used to describe the relationship of apparent clearance and volume of distribution to body weight. The effect of age on these two PK parameters was modeled by an exponential function. Results A one‐compartment disposition with sequential zero and first order absorption model described the data best. Age was a significant covariate to impact the OME apparent clearance. The estimated metabolic maturation half‐life of OME metabolism was approximately one month. Conclusions From single oral dose data in pediatric subjects, it was estimated that OME apparent clearance reached maturation at approximately six months of age when body weight was normalized by an allometric model. Clinical Pharmacology & Therapeutics (2004) 75 , P41–P41; doi: 10.1016/j.clpt.2003.11.154