Population pharmacokinetics of methylphenidate hydrochloride extended-release multiple-layer beads in pediatric subjects with attention deficit hyperactivity disorder

• Published in: Drug design, development and therapy Vol. 9; no. default; pp. 2767 - 2775
• Main Authors: Teuscher, Nathan, Adjei, Akwete, Findling, Robert, Greenhill, Laurence, Kupper, Robert, Wigal, Sharon
• Format: Journal Article
• Language: English
• Published: New Zealand Dove Medical Press Limited 01.01.2015; Taylor & Francis Ltd; Dove Medical Press
• Subjects: Adolescent; Adolescents; Adult; Adults; Age; Age Factors; Analysis; Attention Deficit Disorder with Hyperactivity - drug therapy; Attention deficit hyperactivity disorder; Beads; Bioavailability; Body weight; Central Nervous System Stimulants - administration & dosage; Central Nervous System Stimulants - pharmacokinetics; Chemistry, Pharmaceutical; Child; Child & adolescent psychiatry; Children; Children & youth; Clinical trials; Computer simulation; Controlled release technology; Delayed-Action Preparations; Dosage; Dosage and administration; Dose-Response Relationship, Drug; Drug dosages; Drug metabolism; Drug therapy; Humans; Hyperactivity; Methylphenidate; Methylphenidate - administration & dosage; Methylphenidate - pharmacokinetics; Methylphenidate hydrochloride; Models, Biological; Multilayers; Nonlinear Dynamics; Original Research; Pediatrics; Pharmaceuticals; Pharmacodynamics; Pharmacokinetics; Pharmacology; Plasma; Population; Teenagers; Testing; New York; United States > US; Baltimore Maryland; methylphenidate; MPH-MLR; Aptensio XR; population pharmacokinetics
• ISSN: 1177-8881; 1177-8881
• DOI: 10.2147/DDDT.S83234

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.