Pharmacokinetics and Bioequivalence of Methylphenidate Hydrochloride 10 mg Immediate-Released Tablets in Healthy Thai Volunteers under Fasting Conditions

Abstract

Methylphenidate is a central nervous system stimulant indicated for attention deficit hyperactivity disorder (ADHD) and narcolepsy. Methylphenidate GPO ® had been developed as a generic alternative to Ritalin ® 10 for Thai people. The aims of this study were to characterize pharmacokinetics in Thai population, and to evaluate bioequivalence of Methylphenidate GPO ® to Ritalin ® 10 to support product registration. A comparative dissolution test was performed in four dissolution media, followed by an open-label, randomized, two-way crossover bioequivalence study under fasting conditions. A single dose of the test or reference product was administered in period I and switched over to another product in period II after 7-day washout period. Blood samples were collected at predefined time points over 24 hours after dosing. Plasma concentrations of methylphenidate were quantified using a validated liquid chromatography-mass spectrometry method. The pharmacokinetics was characterized from plasma concentration-time profile following administration of the test and reference formulations. The pharmacokinetic parameters were in agreement with the previously published data. The AUC 0-t , AUC 0−∞ and C max of two methylphenidate 10 mg tablet formulations were statistically compared in 23 healthy Thai volunteers. The analysis of variance (ANOVA) did not show any significant difference between the formulations. The ratios for geometric least-square means and 90% confidence intervals of log-transformed parameters were within the acceptance range of 80.00–125.00%. Both products were generally well tolerated by healthy Thai subjects. Methylphenidate GPO ® and Ritalin ® 10 were bioequivalent in terms of rate and extent of absorption, and could be used interchangeably.