Pharmacokinetics and Bioequivalence of a Novel Extended-Release Formulation of Methylphenidate Hydrochloride for Attention-Deficit/Hyperactivity Disorder

Abstract

Extended-release (ER) formulations of the stimulant methylphenidate are commonly used to treat attention-deficit/hyperactivity disorder in both children and adults. Previous studies have shown that the clinical effectiveness of long-acting methylphenidate formulations is closely tied to the drug's pharmacokinetic (PK) profile, highlighting the need for consistency in drug exposure. ODX-methylphenidate ER uses an osmotic pump design to provide controlled release of drug over the course of the day. In these similarly designed 4-period replicate crossover studies, the PK profile of ODX-methylphenidate ER was compared to the reference product, osmotic release oral system (OROS)-methylphenidate ER, in healthy subjects in the fasted state. In the first trial (N = 60), a single 72-mg tablet of ODX-methylphenidate ER was compared to two 36-mg tablets of OROS-methylphenidate ER, while in the second trial (N = 36), a single 54-mg tablet of ODX-methylphenidate ER was compared to a 54-mg tablet of OROS-methylphenidate ER. The 2 studies had very comparable results, demonstrating similar PK parameters for the 2 products, including during the critical 7-12-hour postdose window. Statistical bioequivalence between the 2 formulations was confirmed for maximum drug concentration, area under the concentration-time curve from time 0 to 3 hours after dosing (AUC0-3 h), AUC from 3 to 7 hours after dosing, AUC from 7 to 12 hours after dosing, and AUC from time 0 extrapolated to infinity in both trials. Safety and tolerability were similar for both products and in both trials, with no serious adverse events reported.