Evolution of stimulants to treat ADHD: transdermal methylphenidate.
OBJECTIVE
The following comprehensive review describes the evolution of stimulant drug formulations used in the treatment of attention-deficit/hyperactivity disorder (ADHD). Emphasis is placed on the basic and clinical pharmacology of the dl-methylphenidate (MPH) transdermal system (MTS).


METHODS
The pharmacokinetic and pharmacodynamic literature pertaining to MPH and amphetamine enantiomers was reviewed in the context of ADHD therapy and MTS as a treatment option.


RESULTS
MTS incorporates MPH into an adhesive monolithic matrix, using the free base form of the drug to facilitate transdermal absorption. MTS technology minimizes contact dermatitis by eliminating to need for percutaneous penetration enhancers. After a lag time of approximately 2 h, plasma concentrations of the therapeutic d-MPH isomer become detectable, then continuously rise over the course of the recommended 9 h wear time. Concentrations of l-MPH typically attain 40-50% that of d-MPH (vs. 1-2% following oral MPH). Unauthorized MTS removal poses some misuse liability and over 50% of MTS drug content remains in the discarded system.


CONCLUSIONS
While liquid or chewable MPH formulations overcome potential swallowing difficulties, as do sprinkled once-daily extended-release (ER) MPH products, only MTS addresses swallowing difficulties while also offering a flexible individualized MPH exposure time in a once-daily MPH regimen.
Patrick
Kennerly S
KS
Department of Pharmaceutical and Biomedical Sciences, Medical University of South Carolina, Charleston, South Carolina 29425-0742, USA. patrickk@musc.edu
Straughn
Arthur B
AB
Perkins
Jeb S
JS
González
Mario A
MA
D000279:Administration, Cutaneous; D000661:Amphetamine / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy*; D000697:Central Nervous System Stimulants / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D002986:Clinical Trials as Topic; D003692:Delayed-Action Preparations; D003877:Dermatitis, Contact / Q000209:etiology; D006801:Humans; D008774:Methylphenidate / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D012869:Skin Absorption; D013237:Stereoisomerism; D013997:Time Factors
D000697:Central Nervous System Stimulants; D003692:Delayed-Action Preparations; D008774:Methylphenidate; D000661:Amphetamine