title: Pharmacokinetic considerations in the treatment of attention-deficit hyperactivity disorder with methylphenidate.
abstract: Methylphenidate is commonly used for the treatment of attention-deficit hyperactivity disorder (ADHD). Its efficacy in improving the core symptoms of ADHD, as well as some of the aggressive and oppositional behaviours, is well documented, based on a large volume of research. Methylphenidate has a wide margin of safety and relatively mild adverse effects, most commonly appetite suppression and insomnia. Methylphenidate is a rapidly absorbed medication that, in its d-isomer form, readily penetrates the CNS, particularly the striatum. It appears to function by blocking the reuptake of dopamine. Both the plasma concentrations and behavioural effects of methylphenidate demonstrate a time to maximum of between 1 and 3 hours, with the maximum behavioural effects occurring when the plasma concentrations are increasing. Because of the rapid onset of action, the effects of methylphenidate can be dramatic but usually last only about 4 hours with the immediate-release formulation. The behavioural responses of individuals are also highly variable, so that it is necessary to start treatment at a low dosage and increase up to a maximally effective dosage (usually starting at 10-15 mg/day with increases of 10-15mg at weekly intervals to a maximum dosage of 60 mg/day, irrespective of formulation). Because of the variability in behavioural responses, assessment of plasma concentrations is not clinically useful nor does weight help in deciding an appropriate dosage. The difficulties in administering methylphenidate multiple times a day, particularly during the school day, have been alleviated in the past few years by the development of extended-release preparations with varying behavioural effects lasting 8-12 hours. The 8-hour preparations (Metadate) CD and Ritalin) LA) utilise a microbead technology, while the 12-hour preparation (Concerta) utilises an osmotic pump system. All extended-release formulations effectively control the symptoms of ADHD. While pharmacokinetic differences appear to exist between some of these new formulations, there are currently no clinical data available to demonstrate clinical efficacy differences between them.
authors.affiliation: University of Oklahoma Health Sciences Center, Child Study Center, Oklahoma City, Oklahoma 73117, USA. mark-wolraich@ouhsc.edu
authors.forename: Mark L
authors.initials: ML
authors.lastname: Wolraich
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Doffing
mesh_terms: D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy / Q000378:metabolism*; D001682:Biological Availability; D000697:Central Nervous System Stimulants / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D004334:Drug Administration Schedule; D006801:Humans; D008774:Methylphenidate / Q000493:pharmacokinetics* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000697:Central Nervous System Stimulants; D008774:Methylphenidate