Akwete Lex Adjei
Rhodes Pharmaceuticals L.P, USA
Title: Steady-state bioavailability of extended-release methylphenidate Capsules vs. immediate-release methylphenidate tablets in healthy adult volunteers
Biography
Biography: Akwete Lex Adjei
Abstract
A novel formulation of extended-release (ER) methylphenidate hydrochloride that utilizes multiple layers of coatings on beads for encapsulation into hard gelatin capsule shells (Aptensio®, MPH-MLR) was evaluated to determine the relative bioavailability vs. immediate-release methylphenidate tablets (IR, Ritalin®) as single and multiple doses in the fed state. A single-center, 4-day, multiple-dose, randomized, open-label, 2-period crossover study design assessed the relative bioavailability of MPH-MLR 80 mg once daily versus Ritalin® IR 25 mg 3 times daily (TID) in 26 healthy adults. Serial blood samples were collected at pre-specified time points over the 4-day dosing period for determination of methylphenidate concentration and pharmacokinetic analyses. Relative bioavailability of MPH-MLR versus Ritalin® (75 mg total daily dose normalized to a single dose of MPH-MLR) as a single dose under fed conditions, and at steady state under fed conditions, was determined based on AUC0-t, AUC0-inf and Cmax of methylphenidate. MPH-MLR administration produced a rapid initial peak, a moderate decline until ~5 hours postdose, and a gradual increase until ~7 hours postdose. Cmax was lower for MPH-MLR 80 mg than methylphenidate IR 25 mg on Day 1. Exposure was similar with 90% CI limits for the geometric mean ratios of log-transformed AUC0-t that were within the 80%-125% equivalence range. Day 4 partial AUC0-4 (74.49±15.23 hr.ng/mL) for MPH-MLR exceeded Ritalin IR 25 mg 3 times daily (66.01±17.41 hr.ng/mL), and therefore was not bioequivalent. MPH-MLR capsules administered once daily and methylphenidate IR administered TID provided comparable maximum methylphenidate concentrations and systemic exposure in the fed state.