title: A Single-Dose, Single-Period Pharmacokinetic Assessment of an Extended-Release Orally Disintegrating Tablet of Methylphenidate in Children and Adolescents with Attention-Deficit/Hyperactivity Disorder.
abstract: To determine the pharmacokinetic (PK) profile of a proprietary formulation of methylphenidate (MPH) in children and adolescents with attention-deficit/hyperactivity disorder (ADHD) in a phase 1 study. Methylphenidate extended-release orally disintegrating tablets (MPH XR-ODTs) combine two technologies in a single-tablet formulation-an extended-release profile that was designed for once-daily dosing in an ODT that does not require water or chewing for ingestion.
  
  
  
  This was a single-dose, open-label, single-period, single-treatment study, in which 32 children with ADHD who were receiving MPH in doses of 40 or 60 mg before beginning the study each received a 60-mg dose (2 × 30 mg) of MPH XR-ODT. The following plasma PK parameters of MPH were determined for participants grouped by age (6-7, 8-9, 10-12, and 13-17 years old): maximum concentration (Cmax), time to maximum concentration (Tmax), elimination half-life (T½), area under the curve from 0 hours to infinity (AUCinf), oral clearance (CL/F), and volume of distribution in the terminal phase (Vz/F). Safety and tolerability were also assessed.
  
  
  
  A total of 32 participants received the study drug. For all participants, plasma concentration-time profiles of MPH exhibited a broad peak after administration of MPH XR-ODT through ∼8 hours, indicating extended release from the formulation, followed by an apparent first-order elimination phase. As age increased, MPH exposure decreased and mean estimates of CL/F increased; however, weight-normalized CL/F values were comparable across age groups. Similarly, mean estimates of Vz/F increased with age, but weight-normalization decreased differences across age groups, with the exception of the youngest age group, which had higher values. All adverse events (AEs) were mild.
  
  
  
  This XR-ODT formulation of MPH demonstrated weight-normalized clearance rates that were consistent across all age groups, a PK profile consistent with once-daily dosing, and an AE profile consistent with this class of medication in children and adolescents with ADHD.
authors.affiliation: 1 Center for Psychiatry and Behavioral Medicine, Inc., Las Vegas, Nevada.
authors.forename: Ann
authors.initials: A
authors.lastname: Childress
authors.affiliation: 2 Department of Psychiatry, Icahn School of Medicine at Mount Sinai , New York City, New York.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Newcorn
authors.affiliation: 3 Worldwide Clinical Trials , Austin, Texas.
authors.forename: Jeffrey G
authors.initials: JG
authors.lastname: Stark
authors.affiliation: 4 Neos Therapeutics, Inc. , Grand Prairie, Texas.
authors.forename: Russ
authors.initials: R
authors.lastname: McMahen
authors.affiliation: 4 Neos Therapeutics, Inc. , Grand Prairie, Texas.
authors.forename: Mark
authors.initials: M
authors.lastname: Tengler
authors.affiliation: 4 Neos Therapeutics, Inc. , Grand Prairie, Texas.
authors.forename: Carolyn
authors.initials: C
authors.lastname: Sikes
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000367:Age Factors; D019540:Area Under Curve; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy*; D000697:Central Nervous System Stimulants / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D002648:Child; D003692:Delayed-Action Preparations; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D008774:Methylphenidate / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D013607:Tablets; D014018:Tissue Distribution
chemical_list: D000697:Central Nervous System Stimulants; D003692:Delayed-Action Preparations; D013607:Tablets; D008774:Methylphenidate