A small preschool study characterized plasma exposure to lisdexamfetamine and its active metabolite, d-amphetamine. Its pharmacokinetic findings provide exposure information; the open-label symptom changes do not establish placebo-controlled efficacy.
Childress and colleagues enrolled 24 children aged four or five years with ADHD in an eight-week, open-label, dose-optimization study. Treatment began at 5 mg lisdexamfetamine and could be titrated up to 30 mg under the research protocol.
Blood samples supported plasma measurements of the parent prodrug and d-amphetamine. Only eight participants comprised the full pharmacokinetic set with sufficiently intensive interpretable sampling. That subset is especially important when considering the precision and generalizability of parameters derived from concentration-time curves.
Exposure to d-amphetamine increased with lisdexamfetamine dose. Mean time to maximum d-amphetamine concentration ranged from about 4.0 to 4.2 hours, while estimated terminal half-life ranged from about 7.2 to 8.5 hours across the reported dose groups.
These parameters describe different features of exposure: peak timing, elimination and total exposure are not interchangeable. They concern d-amphetamine in plasma, rather than an interchangeable value for parent lisdexamfetamine, whole blood, urine or oral fluid. They also do not directly describe how long a particular clinical benefit lasts.
Symptom scores decreased during treatment, but the absence of a placebo group prevents separation of medication effects from expectations, observer effects and other time-related changes. Decreased appetite was reported in eight of the 24 participants, and adverse events led two participants to discontinue at the starting dose.
The study was industry funded, small and brief. It cannot establish rare-event safety or a concentration cutoff for benefit or impairment. Its dosing schedule was investigational evidence, not a personalized dosing recommendation. For forensic interpretation, identifying the active analyte and specimen matrix is necessary before comparing a laboratory result with these pharmacokinetic observations.
Read our analysis of plasma concentration and cognition in a separate controlled experiment.
Lisdexamfetamine Dimesylate for Preschool Children with Attention-Deficit/Hyperactivity Disorder. doi:10.1089/cap.2019.0117.