title: A pharmacokinetic evaluation of oral edivoxetine hydrochloride for the treatment of attention deficit-hyperactivity disorder.
abstract: BACKGROUND
  The majority of available therapeutics to treat attention-deficit/hyperactivity disorder (ADHD) are formulations of either methylphenidate or amphetamine. However, psychostimulants may not be suitable options for many patients. The availability of novel pharmacological agents to treat ADHD is highly desirable. Edivoxetine hydrochloride (LY2216684) is a highly selective and potent norepinephrine reuptake inhibitor under clinical development for ADHD.
  
  
  METHODS
  This paper provides an overview of what is presently known of the pharmacokinetics (PK) of edivoxetine based on available studies in healthy volunteers, in subjects with compromised renal and hepatic functioning and in children and adolescents.
  
  
  CONCLUSIONS
  Available data suggest edivoxetine is safe and well tolerated. Edivoxetine is readily absorbed with metabolism proceeding through the CYP hepatic enzyme pathway, with CYP2D6 and CYP3A4 playing the most prominent roles. The tmax is ∼ 2 h post-dose, and the plasma t1/2 is ∼ 4 - 6 h irrespective of the dose. Pharmacokinetic parameters are not substantially different between children and adults. Edivoxetine may be a promising non-stimulant therapeutic agent. However, at present, there is insufficient data available to permit a thorough analysis of its potential place in ADHD pharmacotherapy, or how its PK and pharmacodynamics may differ in clinically meaningful ways from existing agents.
authors.affiliation: University of Florida, Department of Pharmacotherapy and Translational Research , 1600 SW Archer Road, RM PG-23, Gainesville, FL 32610-0486 , USA.
authors.forename: John S
authors.initials: JS
authors.lastname: Markowitz
authors.forename: Bryan J
authors.initials: BJ
authors.lastname: Brinda
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D018759:Adrenergic Uptake Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000328:Adult; D000367:Age Factors; D000818:Animals; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy*; D002648:Child; D006207:Half-Life; D006801:Humans; D007674:Kidney Diseases / Q000503:physiopathology; D008107:Liver Diseases / Q000503:physiopathology; D009025:Morpholines / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D010626:Phenylethyl Alcohol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use
chemical_list: D018759:Adrenergic Uptake Inhibitors; D009025:Morpholines; C568831:alpha-((5-fluoro-2-methoxyphenyl)methyl)-alpha-(tetrahydro-2H-pyran-4-yl)-2-morpholinemethanol; D010626:Phenylethyl Alcohol
keywords: LY2216684; attention-deficit/hyperactivity disorder; edivoxetine; non-stimulant; pharmacokinetics