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

  title={Bioavailability of modified‐release methylphenidate: influence of high‐fat breakfast when administered intact and when capsule content sprinkled on applesauce},
  author={Lucy M-C Lee and Joanne Kepple and Yibin Wang and Stephen Freestone and Ray Bakhtiar and Yanfeng Wang and Mohammad Rumman Hossain},
  journal={Biopharmaceutics \& Drug Disposition},
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… 

Pharmacokinetics of Methylphenidate After Oral Administration of Two Modified-Release Formulations in Healthy Adults

Results indicate that the recommended starting dose of the Ritalin® LA 20mg capsule formulation provides more rapid absorption and higher peak plasma concentrations than the recommended 18mg starting doses of the Concerta® formulation.

Comparison of the pharmacokinetics and clinical efficacy of new extended-release formulations of methylphenidate

  • R. Maldonado
  • Medicine, Biology
    Expert opinion on drug metabolism & toxicology
  • 2013
This review focuses on the pharmacokinetics of ER MPH formulations (Concerta, Equasym XL/Metadate CD, Medikinet Retard and Ritalin LA) and attempts to align the properties of each agent with available clinical findings in children/adolescents with ADHD.

Pharmacokinetics of AR19, an Immediate-Release Amphetamine Sulfate Formulation Designed to Deter Manipulation for Administration Via Nonoral Routes: Bioequivalence to Reference Racemic Amphetamine Sulfate, Dose Proportionality, and Food Effect.

  • S. CarasT. Sharpe
  • Medicine, Biology
    Journal of child and adolescent psychopharmacology
  • 2019
Objectives: We evaluated the pharmacokinetics (PK) of an investigational immediate-release amphetamine (AMP) sulfate formulation (AR19) designed to deter nonoral administration versus reference

Effectiveness and safety of a long-acting, once-daily, two-phase release formulation of methylphenidate (Ritalin® LA) in school children under daily practice conditions

Evaluated effectiveness of a two-phase release formulation of Ritalin® LA under daily practice conditions in Germany shows significant benefit also under routine practice conditions, in line with clinical trial data.

Application of Physiologically Based Absorption Modeling to Characterize the Pharmacokinetic Profiles of Oral Extended Release Methylphenidate Products in Adults

The model provides a quantitative tool to predict the biphasic plasma time course data for ER MPH, helping elucidate factors responsible for the diverse plasma MPH concentration profiles following oral dosing of different ER formulations.

An update on the pharmacokinetic considerations in the treatment of ADHD with long-acting methylphenidate and amphetamine formulations

Since there are no reliable biomarkers that can predict individualized response to long-acting stimulants, clinicians need to consider their distinctive pharmacokinetic properties, including the pharmacokinetics profile, rate and extent of absorption, variability, dose proportionality, bioequivalence and potential for accumulation.

Efficacy and Safety of a Chewable Methylphenidate Extended-Release Tablet in Children with Attention-Deficit/Hyperactivity Disorder

MHP ERCT 20–60 mg significantly improved ADHD symptoms compared with placebo at 2 hours postdose through at least 8 hours post dose, and was generally safe and well tolerated, with a safety profile consistent with other MPH ER formulations.

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

The psychostimulant dl‐methylphenidate (MPH) remains the most common drug therapy in child and adolescent psychiatry for the treatment of attention‐deficit‐hyperactivity disorder (ADHD). Evidence of

New methylphenidate formulations for the treatment of attention-deficit/hyperactivity disorder

The newly approved resolved enantiomer product d-MPH is now available in an IR formulation, and when administered at one-half the dose to that of the racemate, is purported to produce a longer duration of clinical effect, despite essentially identical pharmacokinetics.



Effect of food on the pharmacokinetics of osmotic controlled‐release methylphenidate HCl in healthy subjects

The results indicate the absence of dose dumping from OROS® (methylphenidate HCl) in the presence of food, and food does not impede drug absorption and OROS ( methylphenidate) may be administered in the fed or fasted state.

Methylphenidate bioavailability in adults when an extended-release multiparticulate formulation is administered sprinkled on food or as an intact capsule.

The bioavailability of methylphenidate was not altered when Metadate CD capsules were administered by sprinkling their contents onto a small amount of applesauce, and the pharmacokinetic profile for Metadates CD exhibited biphasic release characteristics with a sharp initial slope and a second rising portion.

Methylphenidate bioavailability from two extended-release formulations.

The two formulations of d,l-threo-methylphenidate (MPH) from two extended-release products are not bioequivalent and the capsule fonnulation produces greater exposure to MPH and higher MPH concentrations during the first 6 hours following dosing.

The effect of food on the pharmacokinetics of nifedipine in two slow release formulations: pronounced lag-time after a high fat breakfast.

A dosage form-dependent food interaction was observed which, under fed conditions, resulted in pronounced differences in the relative bioavailability of nifedipine between Slofingipine XL and Adalat OROS over the intended dosing interval of 24 h.

Effect of Food on Early Drug Exposure from Extended-Release Stimulants: Results from the Concerta®, Adderall XR™ Food Evaluation (CAFÉ) Study

As a child's or adult's eating pattern varies, methylphenidate exposure over the first 8 h would be expected to have less day-to-day variation compared with amphetamine exposure, providing consistent levels of early drug exposure.

Methylphenidate hydrochloride given with or before breakfast: II. Effects on plasma concentration of methylphenidate and ritalinic acid.

Few differences between the "fed" and "fasted" states were noted, but the statistically significant differences indicated that meals accelerate rather than impede the absorption of methylphenidate.

Effects of Food on Clinical Pharmacokinetics

No rational scientific basis is found to predict the effect of food for a particular chemical entity or a chemical class of therapeutic agents, and a mechanistic understanding of the effects of food may serve as a key to the pharmacokinetic optimisation of patient therapy, both in outpatients and hospitalised patients of various age groups.

Novel drug-delivery systems for hypertension.

Clinical studies of methylphenidate serum levels in children and adults.

Progress is reported on the progress in applying a reliable and sensitive gas chromatography-mass spectrometric assay for MPH in serum to clinical studies of hyperactive children and adults.

Relative efficacy of long-acting stimulants on children with attention deficit-hyperactivity disorder: a comparison of standard methylphenidate, sustained-release methylphenidate, sustained-release dextroamphetamine, and pemoline.

Results revealed generally equivalent and beneficial effects of all four medications, and Dexedrine Spansule and pemoline tended to produce the most consistent effects and were recommended for 10 of the 15 children who were responders to medication.