Single-Dose Pharmacokinetics of HLD200, a Delayed-Release and Extended-Release Methylphenidate Formulation, in Healthy Adults and in Adolescents and Children with Attention-Deficit/Hyperactivity Disorder
| Autor: | Bev Incledon, Jogarao V. S. Gobburu, Shailly Mehrotra, Norberto J. DeSousa, Angus McLean, Ann C. Childress |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Adult
Male Pediatrics medicine.medical_specialty Time Factors Evening Adolescent Cmax Administration Oral methylphenidate attention-deficit/hyperactivity disorder Young Adult 03 medical and health sciences 0302 clinical medicine delayed-release Pharmacokinetics mental disorders medicine Humans Attention deficit hyperactivity disorder Pharmacology (medical) Child extended-release Morning Cross-Over Studies Methylphenidate Age Factors Area under the curve Original Articles Middle Aged medicine.disease 030227 psychiatry Psychiatry and Mental health Tolerability Attention Deficit Disorder with Hyperactivity Area Under Curve Case-Control Studies Delayed-Action Preparations Anesthesia Pediatrics Perinatology and Child Health Central Nervous System Stimulants Female Psychology pharmacokinetics 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Journal of Child and Adolescent Psychopharmacology |
| ISSN: | 1557-8992 1044-5463 |
| DOI: | 10.1089/cap.2017.0044 |
| Popis: | Objective: Current extended-release (ER) formulations of psychostimulants used for treatment of attention-deficit/hyperactivity disorder (ADHD) provide an extended duration of ADHD symptom control; however, the onset of efficacy can be protracted and variable, leaving the early morning untreated. The primary objective was to characterize the single-dose pharmacokinetics and tolerability of HLD200, an evening-dosed, delayed-release (DR) and ER formulation of methylphenidate (MPH), in healthy adults and in adolescents and children with ADHD. Methods: The pharmacokinetics and tolerability of a single, oral evening dose of HLD200 (54 mg) were evaluated in two single-center open-label studies: the first in healthy adults (n = 12) and the second in adolescents (n = 18) and children (n = 11) with ADHD. Primary pharmacokinetic endpoints were the rate and extent of MPH absorption (Cmax and area under the curve [AUC]) and time to peak concentration (Tmax). These parameters were calculated using noncompartmental analysis. Results: HLD200 produced a pharmacokinetic profile characterized by an 8- to 10-hour delay in MPH release, followed by a period of extended controlled release, resulting in an ascending absorption profile that coincided with the early morning and afternoon. Mean values (coefficient of variation [CV]%) of weight-adjusted pharmacokinetic parameters were similar in adults and in adolescents and children with ADHD: Cmax ([ng/mL]/[mg/kg]) was 9.1 (35.2), 8.8 (34.5), and 7.4 (30.1); AUC0–t ([ng · h/mL]/[mg/kg]) was 126.5 (35.5), 129.4 (34.8), and 129.7 (27.3); and Tmax (hours) was 15.6 (11.1), 17.1 (14.5), and 17.7 (14.1), respectively. Intersubject variability in the mean time to achieve ascending plasma MPH concentrations of 2, 3, 4, and 5 ng/mL was low (CV: 7.8%–17.7%). Conclusions: Evening-dosed HLD200 produces the intended DR and ER pharmacokinetic profile that provides a consistent predictable delay in initial MPH release until the early morning, followed by extended release across the day. The body weight-adjusted pharmacokinetics of HLD200 were similar between adults and adolescents and children with ADHD. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|