title: Population pharmacokinetics of methylphenidate hydrochloride extended-release multiple-layer beads in pediatric subjects with attention deficit hyperactivity disorder.
abstract: A new multilayer-bead formulation of extended-release methylphenidate hydrochloride (MPH-MLR) has been evaluated in pharmacokinetic studies in healthy adults and in Phase III efficacy/safety studies in children and adolescents with attention deficit hyperactivity disorder (ADHD). Using available data in healthy adults, a two-input, one-compartment, first-order elimination population pharmacokinetic model was developed using nonlinear mixed-effect modeling. The model was then extended to pediatric subjects, and was found to adequately describe plasma concentration-time data for this population. A pharmacokinetic/pharmacodynamic model was also developed using change from baseline in the ADHD Rating Scale (ADHD-RS)-IV total scores from a pediatric Phase III trial and simulated plasma concentration-time data. During simulations for each MPH-MLR dose level (10-80 mg), increased body weight resulted in decreased maximum concentration. Additionally, as maximum concentration increased, ADHD-RS-IV total score improved (decreased). Knowledge of the relationship between dose, body weight, and clinical response following the administration of MPH-MLR in children and adolescents may be useful for clinicians selecting initial dosing of MPH-MLR. Additional study is needed to confirm these results.
authors.affiliation: PK/PD Associates, Trophy Club, TX, USA.
authors.forename: Nathan S
authors.initials: NS
authors.lastname: Teuscher
authors.affiliation: Rhodes Pharmaceuticals L.P., Coventry, RI, USA.
authors.forename: Akwete
authors.initials: A
authors.lastname: Adjei
authors.affiliation: Department of Psychiatric Services and Research, Kennedy Krieger Institute, Baltimore, MD, USA ; Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Findling
authors.affiliation: Department of Psychiatry, Division of Child and Adolescent Psychiatry, New York State Psychiatric Institute, Columbia University, New York, NY, USA.
authors.forename: Laurence L
authors.initials: LL
authors.lastname: Greenhill
authors.affiliation: Rhodes Pharmaceuticals L.P., Coventry, RI, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Kupper
authors.affiliation: AVIDA Inc., Newport Beach, CA, USA.
authors.forename: Sharon
authors.initials: S
authors.lastname: Wigal
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy*; D000697:Central Nervous System Stimulants / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002626:Chemistry, Pharmaceutical; D002648:Child; D003692:Delayed-Action Preparations; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008774:Methylphenidate / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008954:Models, Biological; D017711:Nonlinear Dynamics
chemical_list: D000697:Central Nervous System Stimulants; D003692:Delayed-Action Preparations; D008774:Methylphenidate
keywords: Aptensio XR™; MPH-MLR; methylphenidate; population pharmacokinetics