A methylphenidate (MPH) extended-release orally disintegrating tablet (MPH XR-ODT) formulation was recently approved for attention-deficit/hyperactivity disorder treatment in children 6 to 17 years of age. This analysis sought to develop a population pharmacokinetic (PK)/pharmacodynamic (PD) model to describe MPH XR-ODT PD-response data in a classroom study and use the model to simulate PD responses for a range of body weights and doses.
The MPH XR-ODT PK/PD model was developed with pediatric and adult PK data from prior studies and efficacy data from a laboratory classroom study in children with attention-deficit/hyperactivity disorder. In these studies, the safety profile of MPH XR-ODT was consistent with other extended-release MPH formulations. The PK/PD model efficacy end point was the Swanson, Kotkin, Agler, M-Flynn, and Pelham Scale Combined score. Body weight effects on MPH clearance and volume of distribution were included in the resulting model. Simulations using the PK/PD model were performed for patients with body weights between 7 and 100 kg and MPH XR-ODT doses of 10 to 60 mg MPH hydrochloride equivalents.
In the PK/PD model, the maximal reduction in the Swanson, Kotkin, Agler, M-Flynn, and Pelham Scale Combined score was approximately 38 units, and the MPH concentration required to achieve 50% of the maximal reduction was 14.24 ng/mL, suggesting favorable efficacy for MPH XR-ODT. Simulations showed a direct correlation between the effective MPH XR-ODT dose and body weight, with heavier participants requiring higher doses for symptom control.
This model may help facilitate the dose-titration process by identifying an effective MPH XR-ODT target dose.
From *Certara, Raleigh, NC; and
†Neos Therapeutics, Grand Prairie, TX.
Received September 29, 2017; accepted after revision June 25, 2018.
Reprints: Nathan S. Teuscher, PhD, Certara, 5511 Capital Center Dr, Suite 204, Raleigh, NC 27606 (e-mail: Nathan.Teuscher@certara.com).
This study was funded by Neos Therapeutics, Inc, and executed by Certara.
Supplemental digital content is available for this article. Direct URL citation appears in the printed text and is provided in the HTML and PDF versions of this article on the journal’s Web site (www.psychopharmacology.com).