Dose‐Proportional Pharmacokinetics of d‐threo ‐Methylphenidate After a Repeated‐Action Release Dosage Form

A bimodal extended‐release formulation of d ‐methylphenidate (d‐MPH) has been developed to enable fast onset of action and once‐daily administration in patients with attention deficit hyperactivity disorder. The authors studied the dose proportionality of extended‐release d ‐MPH pharmacokinetics. Twenty‐five healthy adult volunteers received 5, 10, 20, 30, and 40 mg d ‐MPH in a crossover study with 7 days between doses. All doses were well tolerated. Dose proportionality was shown for all dose‐dependent pharmacokinetic parameters. Geometric means (%gCV) for the first C max peak, C max 0–4 , were 3.25 (29.0%), 6.05 (27.1%), 12.6 (31.9%), 18.5 (31.9%), and 25.2 ng/mL (29.3%) for d ‐MPH 5, 10, 20, 30, and 40 mg, respectively. Geometric means (%gCV) for C max4–10 were 3.18 (27.5%), 5.84 (27.7%), 12.5 (31.7%), 17.7 (31.6%), and 23.6 ng/mL (29.0%), respectively. Geometric means for AUC 0‐∞ were 24.3 (30.7%), 45.9 (30.2%), 96.4 (35.5%), 144 (33.3%), and 195 ng • h/mL (30.9%), respectively. The pharmacokinetics of once‐daily extended‐release d ‐MPH are proportional to the dose.