Pharmacokinetic and pharmacodynamic properties of stimulants: implications for the design of new treatments for ADHD.
In the USA, the stimulant drug methylphenidate (MPH) is used to treat a large number (2 million or more per year) of children with Attention Deficit Hyperactivity Disorder (ADHD). Although the US FDA approved MPH in the 1960s, the pharmacokinetic (PK) properties of serum concentrations of MPH in children with ADHD were not described until the 1980s, and then in only a few cases. Recently, information from drug development programs have increased our knowledge about the serum PK and some pharmacodynamic (PD) characteristics of MPH in ADHD children, and studies based on positron emission tomograpy (PET) in adult volunteers have provided new knowledge about the PK properties of MPH at the primary site of action in the brain. We will review these two topics and use this new information to evaluate the mechanisms of action of MPH.
Swanson
J M
JM
Department of Pediatrics, University of California at Irvine, 19722 MacArthur Boulevard, Irvine, CA 92697-4480, USA. jmswanso@uci.edu
Volkow
N D
ND
D000818:Animals; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy* / Q000523:psychology; D000697:Central Nervous System Stimulants / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D002648:Child; D050483:Dopamine Plasma Membrane Transport Proteins; D006801:Humans; D008562:Membrane Glycoproteins; D049990:Membrane Transport Modulators; D026901:Membrane Transport Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D008774:Methylphenidate / Q000493:pharmacokinetics / Q000627:therapeutic use; D009419:Nerve Tissue Proteins; D014055:Tomography, Emission-Computed
D000697:Central Nervous System Stimulants; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D049990:Membrane Transport Modulators; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D008774:Methylphenidate