Pharmacokinetics of methylphenidate in preschoolers with attention-deficit/hyperactivity disorder.

Abstract

OBJECTIVE:

The aim of this study was to compare the pharmacokinetics of immediate-release methylphenidate (MPH) in preschool and school-aged children with attention-deficit/hyperactivity disorder (ADHD).

METHODS:

Preschool children 4-5 years (n = 14) and school-aged children 6-8 years (n = 9) with diagnoses of ADHD were titrated to an effective dose of MPH based on parent, teacher, and clinician ratings in a protocol specified by the Preschoolers with ADHD Treatment Study (PATS) and then attended a laboratory school where the single morning dose of immediate release MPH was administered. Blood samples for measurement of MPH concentrations were obtained predose, and at 1, 2, 4, and 6 hours postdose. A nonlinear model was used to derive three pharmacokinetic (PK) values for analysis: Peak plasma concentration (C(max)), half-life (t(1/2)), and clearance (CL).

RESULTS:

The two groups did not differ in the mean mg dose of MPH (p = 0.33), or in the weight-adjusted mg/kg dose (p = 0.20). Dose-normalized C(max) was significantly higher (p = 0.003), and clearance was significantly slower (p = 0.0002) in preschool than in school-aged children.

CONCLUSIONS:

In this sample, age significantly affected absorption and metabolism of MPH, so that preschool children had greater exposure than school-aged children to the same weight-adjusted dose. These data suggest additional studies should be performed to characterize age-related differences in PK properties of MPH that may inform practitioners about dosing strategies based on the age and size of children being treated.

• Authors: Sharon B Wigal, Suneel Gupta, Laurence Greenhill, Kelly Posner, Marc Lerner, Kenneth Steinhoff, Tim Wigal, Audrey Kapelinski, Jonathan Martinez, Nishit B Modi, Annamarie Stehli, James Swanson
• Journal: Journal of child and adolescent psychopharmacology (J Child Adolesc Psychopharmacol) Vol. 17 Issue 2 Pg. 153-64 (Apr 2007) ISSN: 1044-5463 [Print] United States
• PMID: 17489710 (Publication Type: Clinical Trial, Comparative Study, Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Central Nervous System Stimulants
• Methylphenidate

Topics

• Age Factors
• Area Under Curve
• Attention Deficit Disorder with Hyperactivity (blood)
• Biological Availability
• Central Nervous System Stimulants (administration & dosage, pharmacokinetics)
• Child
• Child, Preschool
• Dose-Response Relationship, Drug
• Female
• Half-Life
• Humans
• Male
• Methylphenidate (administration & dosage, pharmacokinetics)