title: New methylphenidate formulations for the treatment of attention-deficit/hyperactivity disorder.
abstract: dl-Methylphenidate (MPH) remains the most widely used pharmacological agent in the treatment of attention-deficit/hyperactivity disorder (ADHD). The predominantly dopaminergic mechanism of the psychostimulant actions has become more clearly defined. Neuroimaging and genetic studies are revealing the underlying neuropathology in ADHD. Novel extended-release (ER) MPH formulations now offer drug delivery options to overcome both the short-term actions of immediate-release (IR) MPH and the acute tolerance associated with the first-generation ER-MPH products. These novel MPH products apply proprietary technologies such as OROS (Alza), Diffucaps (Eurand) and SODAS (Elan) to offer both the convenience of once-a-day administration and absorption profiles resembling, to varying degrees, the standard multiple dose schedules of IR-MPH. The pharmacodynamics of the separate MPH enantiomers is in the process of further neuropharmacological characterisation. It is well established that dl-MPH undergoes marked stereoselective metabolism. Although l-MPH exhibits only minimal oral absorption, it may preferentially penetrate the brain, and interacts with ethanol to form the metabolite ethylphenidate. The newly approved resolved enantiomer product d-MPH is now available in an IR formulation, and when administered at one-half the dose to that of the racemate, is purported to produce a longer duration of clinical effect, despite essentially identical pharmacokinetics. A long-acting formulation of d-MPH, which employs the SODAS technology, is in the advanced stages of clinical development.
authors.affiliation: Medical University of South Carolina, Department of Pharmaceutical Sciences, 280 Calhoun St., QF221A, Charleston, SC 29425-0742, USA. patrickk@musc.edu
authors.forename: Kennerly S
authors.initials: KS
authors.lastname: Patrick
authors.forename: Mario A
authors.initials: MA
authors.lastname: González
authors.forename: Arthur B
authors.initials: AB
authors.lastname: Straughn
authors.forename: John S
authors.initials: JS
authors.lastname: Markowitz
mesh_terms: D000818:Animals; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy* / Q000503:physiopathology; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D002986:Clinical Trials as Topic; D003692:Delayed-Action Preparations; D015259:Dopamine Agents / Q000627:therapeutic use*; D018565:Food-Drug Interactions; D006801:Humans; D008774:Methylphenidate / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*; D012737:Sex Factors
chemical_list: D003692:Delayed-Action Preparations; D015259:Dopamine Agents; D008774:Methylphenidate