Pharmacokinetics of methylphenidate in preschoolers with attention-deficit/hyperactivity disorder.
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.
Wigal
Sharon B
SB
Child Development Center,University of California, Irvine, California 92612, USA. sbwigal@uci.edu
Gupta
Suneel
S
Greenhill
Laurence
L
Posner
Kelly
K
Lerner
Marc
M
Steinhoff
Kenneth
K
Wigal
Tim
T
Kapelinski
Audrey
A
Martinez
Jonathan
J
Modi
Nishit B
NB
Stehli
Annamarie
A
Swanson
James
J
D000367:Age Factors; D019540:Area Under Curve; D001289:Attention Deficit Disorder with Hyperactivity / Q000097:blood*; D001682:Biological Availability; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D008774:Methylphenidate / Q000008:administration & dosage / Q000493:pharmacokinetics*
D000697:Central Nervous System Stimulants; D008774:Methylphenidate