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A Pharmacokinetic Study of Methylphenidate Hydrochloride Multilayer Extended-Release Capsules (Aptensio XR®) in Preschool-Aged Children with Attention-Deficit/Hyperactivity Disorder.

Publication ,  Journal Article
Adjei, AL; Chaudhary, I; Kollins, SH; Padilla, A
Published in: Paediatr Drugs
October 2020

OBJECTIVE: This was a single-dose, one-period, multicenter, pharmacokinetic (PK) study to evaluate the PK of methylphenidate (MPH) hydrochloride multilayer extended-release capsules (MPH-MLR) in preschool children aged 4 to < 6 years, previously diagnosed with attention-deficit/hyperactivity disorder (ADHD), and on a stable dose of MPH. METHODS: Preschool-aged children (N = 10) received a single oral dose of MPH-MLR (10, 15, or 20 mg) sprinkled over applesauce; a dose equivalent to their pre-enrollment daily dose of MPH. Blood samples for the measurement of MPH concentrations were obtained pre-dose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 24 h post-dose. No structural model was assumed in the derivation of PK values for analysis. Maximum plasma concentration (Cmax), area under the concentration-time curve (AUC), elimination half-life, clearance (CL), and volume of distribution (Vd) data were compared with a historical group of older children aged 6-11 years (N = 11) and analyzed by bodyweight. Safety (adverse event monitoring, vital signs, electrocardiogram, clinical laboratory testing, physical examination) was assessed. RESULTS: Mean dose-normalized Cmax and area under the curve to the last measurable observation (AUC0-t) values were similar across dose groups, ranging from 0.67 ng/mL/mg (MPH 15 mg) to 0.81 ng/mL/mg (MPH 10 mg) for Cmax/dose, and from 7.80 h × ng/mL/mg (MPH 20 mg) to 8.92 h × ng/mL/mg (MPH 10 mg) for AUC0-t/dose. PK results were integrated into a previously described pharmacostatistical population PK model. Visual predictive check plots showed greater variability in the 6- to 11-year-old group than the 4- to < 6-year-old group, and CL increased with increasing body weight in a greater than dose-proportional manner. Mean CL, normalized for body weight, was constant for all dose groups, ranging from 4.88 L/h/kg to 5.80 L/h/kg. Median time to Cmax ranged from 2.00 to 3.00 h post-dose, and overall, dose-normalized Cmax concentrations indicated greater systemic exposures of MPH-MLR in preschool children aged 4 to < 6 years compared with children aged 6-11 years. Children aged 4 to < 6 years had a lower Vd than children aged 6-11 years. There were no unexpected safety signals. CONCLUSION: The PK of MPH-MLR in preschool children demonstrated the biphasic absorption profile described earlier in older children, and the PK profile in children with ADHD aged 4 to < 6 years was similar to the profile in those aged 6-11 years, apart from a lower Vd and relatively higher systemic MPH levels for children in the preschool group. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT02470234.

Duke Scholars

Published In

Paediatr Drugs

DOI

EISSN

1179-2019

Publication Date

October 2020

Volume

22

Issue

5

Start / End Page

561 / 570

Location

Switzerland

Related Subject Headings

  • Pediatrics
  • Models, Biological
  • Methylphenidate
  • Male
  • Humans
  • Female
  • Delayed-Action Preparations
  • Child, Preschool
  • Child
  • Central Nervous System Stimulants
 

Citation

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Adjei, A. L., Chaudhary, I., Kollins, S. H., & Padilla, A. (2020). A Pharmacokinetic Study of Methylphenidate Hydrochloride Multilayer Extended-Release Capsules (Aptensio XR®) in Preschool-Aged Children with Attention-Deficit/Hyperactivity Disorder. Paediatr Drugs, 22(5), 561–570. https://doi.org/10.1007/s40272-020-00409-z
Adjei, Akwete L., Inder Chaudhary, Scott H. Kollins, and Americo Padilla. “A Pharmacokinetic Study of Methylphenidate Hydrochloride Multilayer Extended-Release Capsules (Aptensio XR®) in Preschool-Aged Children with Attention-Deficit/Hyperactivity Disorder.Paediatr Drugs 22, no. 5 (October 2020): 561–70. https://doi.org/10.1007/s40272-020-00409-z.
Adjei, Akwete L., et al. “A Pharmacokinetic Study of Methylphenidate Hydrochloride Multilayer Extended-Release Capsules (Aptensio XR®) in Preschool-Aged Children with Attention-Deficit/Hyperactivity Disorder.Paediatr Drugs, vol. 22, no. 5, Oct. 2020, pp. 561–70. Pubmed, doi:10.1007/s40272-020-00409-z.
Journal cover image

Published In

Paediatr Drugs

DOI

EISSN

1179-2019

Publication Date

October 2020

Volume

22

Issue

5

Start / End Page

561 / 570

Location

Switzerland

Related Subject Headings

  • Pediatrics
  • Models, Biological
  • Methylphenidate
  • Male
  • Humans
  • Female
  • Delayed-Action Preparations
  • Child, Preschool
  • Child
  • Central Nervous System Stimulants