Relative Bioavailability of Methylphenidate Extended-release Chewable Tablets Chewed Versus Swallowed Whole

Purpose

Methylphenidate hydrochloride extended-release chewable tablet (MPH ERCT) is approved for treatment of attention deficit hyperactivity disorder in patients aged 6 years and older. This article evaluates the pharmacokinetic parameters and relative bioavailability of MPH ERCT when chewed versus swallowed whole.

Methods

In this open-label, single-dose, 3-period, 3-treatment crossover study, 12 healthy adult volunteers were randomly assigned to treatment sequence. In each period, subjects received a single 40-mg dose of the assigned treatment (MPH ERCT chewed, MPH ERCT swallowed whole, or methylphenidate extended-release oral suspension MEROS]). Blood samples for pharmacokinetic analysis were collected for 24 hours postdose. Key pharmacokinetic parameters included C_max, AUC_0–t, and AUC_0–∞.

Findings

The geometric mean values for AUC_0–t, AUC_0–∞, and C_max were similar for MPH ERCT chewed, MPH ERCT swallowed whole, and MEROS. In all pairwise between-treatment comparisons, the 90% CIs of the geometric mean ratios for AUC_0–t, AUC_0–∞, and C_max were fully contained within the bioequivalence range of 80% to 125%. Early exposure over the first 4 hours after dosing (AUC_0–4) was similar for MPH ERCT chewed versus swallowed whole; AUC_0–4 was approximately 15% lower for MPH ERCT, either chewed or swallowed, compared with MEROS. Each treatment was generally well tolerated.

Implications

There was no difference in overall rate or extent of exposure of methylphenidate when MPH ERCT was chewed versus swallowed whole by healthy volunteers.