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Population pharmacokinetic analysis of atomoxetine in pediatric patients
Author(s) -
Witcher J.,
Kurtz D.,
Heathman M.,
Sauer J.,
Smith B.
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.2003.11.173
Subject(s) - atomoxetine , dosing , pharmacokinetics , cyp2d6 , medicine , volume of distribution , population , physiologically based pharmacokinetic modelling , cmax , clinical pharmacology , pharmacology , attention deficit hyperactivity disorder , psychiatry , methylphenidate , environmental health , cytochrome p450 , metabolism
Atomoxetine is a novel treatment of ADHD in children, adolescents, and adults. The purpose of this analysis was to characterize atomoxetine pharmacokinetics and the potential influence of patient factors in pediatric patients. A population pharmacokinetic model was developed using the combined sparse and serial plasma data of 420 patients with 2354 observations from 5 pediatric studies. Patient factors with clinical and demographic significance were identified a priori and evaluated on model parameters. The final model was a 1‐compartment model and was validated using several methods. Covariates retained in the final model included CYP2D6 genotype, body weight, and food consumption. The results demonstrate linear pharmacokinetics across the dose range evaluated of 5 to 45 mg twice‐daily. CYP2D6 poor metabolizers had a 9‐fold lower clearance compared to extensive metabolizers. Clearance and volume of distribution increased nearly proportional to increased body weight, indicating dosing based on body weight is appropriate. Simulations showed that weight‐based dosing provides a more narrow and predictable range of exposures in patients. Food consumption decreased the rate of atomoxetine absorption, however the decrease (9% lower Cmax) was deemed clinically insignificant. Age, gender, ethnic origin, and caffeine consumption did not influence atomoxetine disposition. This analysis provided valuable data concerning these patient factors in the target patient population. Clinical Pharmacology & Therapeutics (2004) 75 , P46–P46; doi: 10.1016/j.clpt.2003.11.173