Population Pharmacokinetic-Pharmacodynamic Modeling of Variable Wear Times for a Dextroamphetamine Transdermal System

• Published in: CNS spectrums 2023-04, Vol.28 (2), p.246-246
• Main Authors: Castelli, Mariacristina, Komaroff, Marina, Meeves, Suzanne, Balakrishnan, Kanan, Baron, Kyle T., Mondick, John T., Faraone, Stephen V., Mattingly, Gregory W.
• Format: Article
• Language: English
• Subjects: Abstracts; Pharmacodynamics; Pharmacokinetics; Teenagers
• ISSN: 1092-8529; 2165-6509
• DOI: 10.1017/S1092852923001827

IntroductionThe Dextroamphetamine Transdermal System (d-ATS) was developed as an alternative to oral amphetamine (AMP) formulations for ADHD. In a pivotal study, d-ATS met primary and secondary efficacy endpoints for ADHD in children and adolescents. Study subjects wore d-ATS for 9 hours, and an improvement in Swanson, Kotkin, Agler, M-Flynn, and Pelham scale (SKAMP) total score was observed from 2 through 12 hours after application. Patients with ADHD may need varying durations of treatment for symptoms from day to day. This analysis describes the exposure-response (E-R) relationship for d-ATS and explores possible outcomes for wear times ≤9 hours under varying assumptions.MethodsA population pharmacokinetic (PK) model was developed to describe AMP disposition following d-ATS administration. This model was used to construct a population pharmacokinetic/pharmacodynamic (PK/PD) model from SKAMP total score data from two pediatric clinical studies to characterize onset and duration of effect after d-ATS administration. The integrated PK/PD model was used to describe the d-ATS E-R relationship and simulate the potential onset and duration of effect of d-ATS in response to various removal times (when