Comparative Bioavailability of Methylphenidate Powder for Prolonged-Release Oral Suspension and Methylphenidate Prolonged-Release Chewable Tablets versus Methylphenidate Immediate-Release Tablets: Phase 1, Single-Dose, Randomised, Crossover Studies in Healthy Adults.

BACKGROUND: Various oral methylphenidate formulations are available to treat attention-deficit/hyperactivity disorder, but unmet needs still exist, particularly for individuals with swallowing difficulties or those requiring more flexible dosing options. Two phase 1 studies evaluated the comparative bioavailability and safety/tolerability of two prolonged-release (PR) methylphenidate formulations, an oral suspension and a chewable tablet, compared with an established immediate-release (IR) oral tablet formulation. METHODS: Healthy volunteers were randomised to receive a single dose of methylphenidate PR oral suspension (total dose 60 mg; study 1) or chewable tablet (total dose 40 mg; study 2) and methylphenidate IR tablets (total dose 60 mg in study 1 and 40 mg in study 2) in a crossover manner, with a 7-day washout between treatment periods. Blood samples were collected over the 24-h post-administration period. Comparative bioavailability was defined as the 90% confidence interval (CI) of the relative mean plasma D-methylphenidate area under the plasma concentration-time curve from zero to last measurable concentration (AUClast) of methylphenidate PR formulation to methylphenidate IR being between 80 and 125%. Adverse events (AEs) were documented. RESULTS: In total, 24 individuals (mean age 39-42 years, approximately 50% male) were randomised in each study, of whom 23 received methylphenidate PR oral suspension in study 1 and 23 received methylphenidate PR chewable tablets in study 2; 24 received methylphenidate IR tablets in each study. The relative mean plasma D-methylphenidate AUClast ratios for methylphenidate PR formulation to methylphenidate IR tablets had 90% CIs of 82.30-87.18% in study 1 and 90.01-97.52% in study 2. Treatment-emergent AEs were reported in 26% and 22% of participants receiving the oral suspension and chewable tablets, respectively (versus 50% and 33% of those receiving the IR tablets in the respective studies). These AEs were typical of orally administered methylphenidate, mild in severity and, in general, resolved prior to study end. CONCLUSIONS: The methylphenidate PR oral suspension and chewable tablet formulations are bioequivalent in terms of the total extent of exposure (AUClast) to methylphenidate IR tablets and are tolerable in healthy adults.