Methylphenidate Transdermal System In Attention-Deficit Hyperactivity Disorder in Children
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Drugs 2006; 66 (8): 1127-1128 0012-6667/06/0008-1127/$44.95/0 © 2006 Adis Data Information BV. All rights reserved.
Methylphenidate Transdermal System In Attention-Deficit Hyperactivity Disorder in Children A Viewpoint by Raul R. Silva New York University School of Medicine, New York, New York, USA
Stimulants have been the mainstay of pharmacological treatment for attention-deficit hyperactivity disorder (ADHD) since the late 1930s.[1] Methylphenidate (MPH) preparations are the most frequently used psychostimulants.[2] The majority of MPH products are racemic mixtures of the d- and lisomers of threo-methylphenidate. For many years, the available products had a truncated duration of action necessitating multiple administrations over the course of the day. During the past few years a number of oral methylphenidate preparations (Concerta®, Metadate CD®, Ritalin LA®, and Focalin XR®)1 have been introduced into the market employing technologies that permit the extended release of this otherwise short-acting agent. Capitalising on the differences between these products, in terms of their delivery systems and the proportions of the doses that are released over the day, may help clinicians tailor treatment decisions to patients’ individual needs. The US FDA recently approved the use of the methylphenidate patch in paediatric age groups who suffer from ADHD. The water-resistant methylphenidate patch uses a novel technology to deliver this product. It is referred to as a DOT Matrix™ technology, with a silicone layer that serves to adhere the patch to the skin, and an acrylic component that holds the active substance (MPH) for release. This new version of the patch seems to have lower rates of skin irritation than those reported with earlier patch technologies. A study that examined the skin sensitivity issue compared the DOT Matrix™ MPH patch to a placebo transdermal system (PTS) patch and revealed lower rates of irritation than the control condition (1.3% for MPH patch vs 2.5% for PTS patch), implying skin sensitivity may be due to the patch itself and not the medication it contains.[3] 1
The patches are available in 12.5–37.5 cm2 sizes, and deliver dosages ranging from 12.3 to 31.3 mg/ day, which are intended to be released over ≈9 hours. With the patch being applied for this amount of time, maximal plasma concentrations are achieved in about 8 hours (median); 31% lower plasma concentrations have been reported when the patch is applied to areas such as scapula rather than the patch’s recommended application site, the hip.[4] An interesting difference between this product and orally administered racemic mixtures seems to exist in their pharmacokinetic profiles.[5] With the patch, d- to l- isomer plasma level ratios are in the order of ≈2 : 1 for parameters such as peak plasma concentration and area under the plasma concentration-time curve. This is in contrast to the 10-fold differences evident with oral administration of MPH.[6] One would have to question the potential role of the plasma isomeric discrepancy on the high
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