Pharmacokinetics and safety study of methylphenidate hydrochloride sustained-release tablets in Chinese healthy...

This study aims to investigate the pharmacokinetic (PK) properties and safety of generic versus brand-name methylphenidate hydrochloride (MPH) sustained-release tablets (Concert®) under fasting and fed conditions, and to evaluate bioequivalence between the two formulations, thereby providing sufficient evidence for an abbreviated new drug application. A randomized, open-label, single-dose, four-period, fully replicated crossover bioequivalence study was conducted on healthy Chinese volunteers under fasting and fed conditions (n = 36). Eligible Participants received 18 mg test (T) or reference (R) MPH sustained-release tablets, followed by a 7-day washout interval for each period. Blood samples were collected predose through 72 h postdose. The plasma concentration of methylphenidate was analyzed by validated LC-MS/MS. Bioequivalence evaluation included C_max, AUC_0-∞. Furthermore, owing to the biphase distribution profile of this formulation attributed to the osmotic release oral system (OROS) technology, a partial AUCs (AUC_0-4h,AUC_4-8h ,AUC_8-12h,AUC_0-24h for fed and AUC_0-3h,AUC_3-7h,AUC_7-12h,AUC_0-24h for fasting condition) analysis is necessary. Under both conditions, the T and R formulations showed comparable pharmacokinetics. The geometric mean ratios with 90% confidence interval (CI) were as follows: under fasting conditions, C_max was 91.57-101.48%, AUC_0-∞ was 99.85-106.45%; under fed conditions, these values were 89.88-98.22% and 97.87-103.03%, respectively. Additionally, the partial AUCs results for both fasting and fed trials were consistent. All confidence intervals fell within the 80-125% bioequivalence range. Both formulations demonstrated good tolerability, with no serious adverse events observed. Under both fasting and fed conditions, the test formulation demonstrated bioequivalence to the reference formulation in healthy Chinese Participants. Both preparations were safe and well-tolerated.