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Pharmacokinetics of Mixed Amphetamine Salts Extended Release in Adolescents With ADHD

Published online by Cambridge University Press:  07 November 2014

William G. Kramer ,
Stephanie C. Read ,
Bao-Van Tran ,
Yuxin Zhang  and
Simon J. Tulloch
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Abstract

Objective

A randomized, open-label, single-dose, three-treatment, three-period, crossover, phase I study was conducted to assess the pharmacokinetics of mixed amphetamine salts extended release (MAS XR) in adolescents with attention-deficit/hyperactivity disorder (ADHD).

Methods

Two cohorts of healthy adolescents 13–17 years of age with ADHD were enrolled in the study. Seventeen subjects, weighing ≤75 kg (≤ 65 lbs), were randomized to one of three dosing sequence groups (a single oral dose of MAS XR 10, 20, or 40 mg, follwed by crossover to the alternate treatments, with a 7-day washout between treatments). Six additional subjects, weighing >75 kg (>165 lbs), were randomized simihrly but received larger doses of MAS XR (20, 40, and 60 mg). Blood samples were collected before and at hours 1–12 after drug administration, as well as before and at hours 14, 24,48, and 60.

Findings

Linear pharmacokinetics of dextroamphetamine (D-amphetamine) and loamphetamine (L-amphetamine) were observed with MAS XR in both cohorts. The pharmacokinetics of D-amphetamine and L-amphetamine did not differ between male and female adolescents. A significant decrease in maximum exposure (Cmax) and increase in half-life were seen for both isomers with increasing age, but overall exposure (AUC∞ was not affected. Cmax and AUC∞ for both isomers decreased as body weight increased.

Conclusion

Exposure to MAS XR was linear and directly proportional to the dose administered in 13–17-year-old adolescents with ADHD. The time course of drug absorption and elimination did not appear to be affected by dose at 10–40 mg in subjects weighing ≤75 kg, and at 20–60 mg in subjects weighing >75 kg. Gender did not affect the pharmacokinetics of MAS XR; age and body weight influenced the profile of certain pharmacokinetic variables.

Type
Academic Supplement
Information
CNS Spectrums , Volume 10 , Issue S15: Mixed Amphetamine Salts Extended Release for the Treatment of ADHD in Adolescents: Current Evidence , October 2005 , pp. 6 - 13
Copyright
Copyright © Cambridge University Press 2005

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