Steady-state bioavailability of extended-release methylphenidate (MPH-MLR) capsule vs. immediate-release methylphenidate tablets in healthy adult volunteers.

OBJECTIVES: The objective of the study was to determine the relative bioavailability of an extended-release multilayer bead formulation of methylphenidate hydrochloride (MPH-MLR) 80 mg vs. methylphenidate immediate-release (IR; Ritalin(®)) tablets as single and multiple doses in the fed state. METHODS: A single-center, multiple-dose, randomized, open-label, two-period crossover study conducted in 26 healthy adults assigned to 4 days of once-daily MPH-MLR 80 mg or IR methylphenidate 25 mg three times daily. RESULTS: MPH-MLR 80 mg produced reproducible biphasic profiles of plasma methylphenidate concentrations characterized by a rapid initial peak, followed by a moderate decline reaching a plateau ~5 h post dose, then a gradual increase culminating in an attenuated second peak ~7 h post dose. Maximum concentration was lower for MPH-MLR 80 mg than IR methylphenidate 25 mg three times daily on day 1 (23.70 vs. 31.47 ng/mL); exposure was similar. The geometric mean ratios (MPH-MLR/IR methylphenidate [90 % CI]) of log-transformed area under the plasma drug concentration-time curve to the last measurable observation (day 1: 0.88 [84.75-91.80]; day 4: 0.84 [81.16-86.94]), and area under the plasma drug concentration extrapolated to infinity (day 1: 0.93 [88.57-97.28]; day 4: 0.88 [84.48-91.17]) were within the 80-125 % bioequivalence range. The mean ± SD MPH-MLR 80-mg capsule day 4 area under the plasma drug concentration vs. time curve from 0 to 4 h (74.5 ± 15.2 ng·h/mL) was greater than IR methylphenidate 25 mg three times daily (66.0 ± 17.4 ng·h/mL), confirming steady-state levels during the study period. All treatment regimens were safe and well tolerated. CONCLUSION: MPH-MLR 80-mg capsule once daily or IR methylphenidate 25 mg three times daily provides comparable maximum methylphenidate concentrations and systemic exposure in the fed state.

Duke Scholars

Author Scott Haden Kollins Psychiatry, Child & Family Mental Health & Community Psychia ...