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 (AUC 0‐3 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.