Clinical drug investigation · 2025
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.
СтатьяРандомизированное исследованиеКлиническое исследование I фазыСравнительное исследованиеНазвание и аннотация: Перевод в очереди
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Ramos-Quiroga Josep Antoni, Forcadell Ferré Marta, Schneider-Pérez Alex, Bouhajib Mohammed
Аннотация
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.
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.