New methylphenidate formulations for the treatment of attention-deficit/hyperactivity disorder

• Published in: Expert opinion on drug delivery Vol. 2; no. 1; p. 121
• Main Authors: Patrick, Kennerly S, González, Mario A, Straughn, Arthur B, Markowitz, John S
• Format: Journal Article
• Language: English
• Published: England 01-01-2005
• Subjects: Animals; Attention Deficit Disorder with Hyperactivity - drug therapy; Attention Deficit Disorder with Hyperactivity - physiopathology; Biological Availability; Chemistry, Pharmaceutical; Clinical Trials as Topic; Delayed-Action Preparations; Dopamine Agents - therapeutic use; Food-Drug Interactions; Humans; Methylphenidate - chemistry; Methylphenidate - pharmacokinetics; Methylphenidate - therapeutic use; Sex Factors
• ISSN: 1742-5247
• DOI: 10.1517/17425247.2.1.121

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.