Bioavailability of modified‐release methylphenidate: influence of high‐fat breakfast when administered intact and when capsule content sprinkled on applesauce

Abstract

Ritalin, an immediate release form of racemic methylphenidate hydrochloride, has been available in the USA since 1955 and is used for the treatment of ADHD. The objective of this study was to evaluate the pharmacokinetics of modified-release methylphenidate (highest single dose), Ritalin LA, when administered under fasting condition, with a high-fat breakfast, and when sprinkled on applesauce in healthy adult subjects. Blood samples were drawn for 24 h following a 40 mg oral administration. Most subjects appeared to produce a bimodal methylphenidate plasma concentration profile. In all three treatment groups, methylphenidate was rapidly absorbed with an initial average t(max(0-4)) of 1.3-2.4 h and an average peak plasma concentration [C(max(abs))] of 14.4-15.2 ng/ml. On average, both the rate [C(max(abs)) and t(max(abs))] and the extent of absorption (AUC(0- infinity)) of methylphenidate were similar when the capsule was given with a high fat breakfast and when the capsule contents were sprinkled onto applesauce, compared with the fasting state. No dose dumping was observed when the capsule was given with a high fat breakfast or when sprinkled onto applesauce. The dose was safe and generally well tolerated. Coadministration of a single oral dose of 40 mg methylphenidate capsule whether administered intact with a high-fat breakfast or sprinkled on applesauce did not affect the overall rate or extent of absorption of methylphenidate compared with the fasted condition.

In vitro dissolution and in vivo oral absorption of methylphenidate from a bimodal release formulation in healthy volunteers

“…The twopeak plasma concentration-time profiles are very similar to that reported previously conducted under similar experimental conditions in adults [11][12][13] and in children [11]. The C max and AUC values in the present study (40 mg) are also similar to those reported previously at a lower dose 20 mg [11] after correction for the dose differences.…”

A randomized, rater-blinded, crossover study comparing the clinical efficacy of Ritalin® LA (methylphenidate) treatment in children with attention-deficit hyperactivity disorder under different breakfast conditions over 2 weeks

“…This trial thus corroborates the pharmacokinetic studies, which pointed out the potential advantage for Ritalin Ò LA of not being influenced by food intake (Lee et al 2003;Haessler et al 2008). Remarkably, this independence of food has been confirmed by several raters in different categories that often have a different view of medication effects: teachers, parents and physicians independently agreed that there is no difference in efficacy regardless of the breakfast group.…”

“…For Ritalin Ò LA, it has been shown that a high-fat breakfast has only a negligible effect on the bioavailability when compared to a standard breakfast (Lee et al 2003). In a previous study, comparing the pharmacokinetics of Ritalin Ò LA and Medikinet Ò retard, it could be shown that Ritalin Ò LA exerted its biphasic profile under both fasted and fed conditions with a standard continental breakfast, while Medikinet Ò retard lost the retardation in the fasted state (Haessler et al 2008).…”

Advances in the Pharmacotherapy of Attention‐Deficit‐Hyperactivity Disorder: Focus on Methylphenidate Formulations

“…10,136 Ritalin LA capsules can be opened and sprinkled on applesauce if needed without altering the pharmacokinetic profile. 139 Ritalin LA may be given without regard to food, although, as with the other modified-release MPH formulations, high-fat meals may delay the T max by approximately 1 hour. The overall extent of absorption is not significantly affected by food.…”

“…The overall extent of absorption is not significantly affected by food. 139 Ritalin LA is available in 20-, 30-, and 40-mg capsule strengths (Table 3).…”