Methylphenidate blood levels and therapeutic response in children with attention-deficit hyperactivity disorder: I. Effects of different dosing regimens.
OBJECTIVE
Methylphenidate (MPH) is a drug of choice for treating attention-deficit/hyperactivity disorder (ADHD), although its use has been complicated by its short duration of action. The development of ideal long-acting preparations requires detailed understanding of the pharmacokinetic and pharmacodynamic consequences of complex dosing regimens. The purpose of this study was to ascertain if administration paradigms that produce stable or rising MPH levels alter the rate with which MPH is absorbed, and to determine how effectively long-acting administration paradigms compare with thrice daily administration of immediate-release MPH.


METHODS
Forty-eight boys diagnosed with ADHD (mean age 10.6 +/- 1.1 year) participated in this double-blind, parallel group study to evaluate the pharmacokinetics and efficacy and of 1 mg/kg/day MPH administered in five different paradigms and placebo. Objective measures of activity and attention (McLean Motion Attention Test; M-MAT) and plasma measures of d- and l-MPH were obtained hourly during the course of a 12-hour laboratory session.


RESULTS
The rate of absorption and elimination of d-MPH was dependent on the pattern of administration, particularly on the initial bolus concentration. This suggests that d-MPH may act on the gastrointestinal system to slow absorption of additional d-MPH. There were significant differences among regimens on time course and degree of therapeutic response. Pulsatile administration produced greater improvement than escalating levels.
Teicher
Martin H
MH
Department of Psychiatry, Harvard Medical School, Boston, Massachusetts., Developmental Biopsychiatry Research Program, McLean Hospital, Belmont, Massachusetts, USA. martin_teicher@hms.harvard.edu
Polcari
Ann
A
Foley
Mary
M
Valente
Elizabeth
E
McGreenery
Cynthia E
CE
Chang
Wei-Wei
WW
McKay
Gordon
G
Midha
Kamal K
KK
D001288:Attention / Q000187:drug effects; D001289:Attention Deficit Disorder with Hyperactivity / Q000097:blood* / Q000188:drug therapy*; D000697:Central Nervous System Stimulants / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D002648:Child; D015897:Comorbidity; D003692:Delayed-Action Preparations; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D008774:Methylphenidate / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D009043:Motor Activity / Q000187:drug effects; D009483:Neuropsychological Tests; D020551:Pulse Therapy, Drug; D013237:Stereoisomerism
D000697:Central Nervous System Stimulants; D003692:Delayed-Action Preparations; D008774:Methylphenidate