A Single‐Dose, Two‐Way Crossover, Bioequivalence Study of Dexmethylphenidate HCl with and without Food in Healthy Subjects

  title={A Single‐Dose, Two‐Way Crossover, Bioequivalence Study of Dexmethylphenidate HCl with and without Food in Healthy Subjects},
  author={Steve K. Teo and Michael R. Scheffler and Anfan Wu and David I. Stirling and Steve D. Thomas and Daria Stypinski and Vikram D. Khetani},
  journal={The Journal of Clinical Pharmacology},
Attention deficit hyperactivity disorder (ADHD) in children is effectively treated by racemic oral methylphenidate (dl‐MPH). The d‐isomer (d‐MPH) has been developed as an improved treatment for ADHD since only half the racemic dose is used. This study, performed in healthy subjects, assessed the effect of food on the pharmacokinetics of dexmethylphenidate hydrochloride (d‐MPH HCl) in a single dose (2 × 10‐mg tablets), two‐way crossover with d‐MPH administered to subjects in both a fasting state… 

Pharmacokinetics and therapeutic effect of OROS methylphenidate under different breakfast conditions in children with attention-deficit/hyperactivity disorder.

It is demonstrated that in children with attention-deficit/hyperactivity disorder, administering OROS MPH with or without food produces similar PK and PD profiles, as demonstrated by the Swanson, Kotkin, Agler, M-Flynn, and Pelham Attention and Deportment measures and global assessments.

Absorption Differences between Immediate-Release Dexmethylphenidate and dl-Methylphenidate

The AUC0–3 h difference reported here points to the potential limitations of using bioequivalence for sound predictions of dose-response relationships, and knowledge of the greater early exposure to d-MPH after the pure d-isomer drug compared with the racemate may contribute to drug individualization/optimization in the treatment of attention deficit hyperactivity disorder.

Methylphenidate blood levels and therapeutic response in children with attention-deficit hyperactivity disorder: I. Effects of different dosing regimens.

The rate of absorption and elimination of d- MPH was dependent on the pattern of administration, particularly on the initial bolus concentration, which suggests that d-MPH may act on the gastrointestinal system to slow absorption of additional d-MKH.

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.

Dexmethylphenidate extended-release capsules for the treatment of attention deficit hyperactivity disorder

The extended-release form of methylphenidate, developed using proprietary Spheroidal Oral Drug Absorption System technology, is approved for the treatment of attention deficit hyperactivity disorder in individuals as young as 6 years old.

Differential pharmacokinetics and pharmacodynamics of methylphenidate enantiomers: does chirality matter?

Data from in vitro, animal, and human studies support the premise that the d-enantiomer of MPH mediates the neurophysiological actions of MPH and therefore likely mediates its clinical efficacy.

Attention-Deficit Hyperactivity Disorder

The efficacy and safety of five of the more novel long-acting pharmacological treatments recently approved by the FDA for marketing in the US for paediatric ADHD, along with an α2-adrenoceptor agonist in preparation are considered.

Dexmethylphenidate hydrochloride in the treatment of attention deficit hyperactivity disorder

This paper reviews and summarizes the available research literature on d-MPH regarding pharmacodynamic, pharmacokinetic, chemical structure, receptor binding, toxicology, and clinical perspectives and potentially may offer some advantages in the realms of absorption and duration of action compared with its racemic counterpart.

Methylphenidate and its Isomers

It is concluded that d-threo-methylphenidate, which is the more potent and abundant of the two isomers, is the major contributor of both efficacy and adverse effects, irrespective of the formulation or route of administration of the racemate.



Enantioselective pharmacokinetics and pharmacodynamics of dl‐thero‐mcthylphenidate in children with attention deficit hyperactivity disorder

The computer tests revealed a drug‐induced improvement in sustained attention that was entirely attributable to the d‐enantiomer, and there was no evidence to suggest that the effectiveness of d‐methylphenidate was in any way compromised by the presence of its antipode.

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.

Effects of Food on the Pharmacokinetics of Methylphenidate

Testing the hypothesis that the pharmacokinetics of d-meth- ylphenidate (d-MPH) would be altered by food ingested before administration of an immediate release formulation but not when food is ingested before a slow release formulation found no effect on rate of absorption.

Enantioselective Pharmacokinetics of dl-threo-Methylphenidate in Humans

It was found that chewing the slow release formulation led to a pharmacokinetic profile very similar to that of MPH-IR, suggesting that MPH-SR should not be prescribed for children who chew tablets.

Stereoselective urinary pharmacokinetics of dl-threo-methylphenidate and its major metabolite in humans.

Observations suggest that, after oral administration of dl-MPH, the distortion in the ratio of MPH or RA enantiomers in urine samples was attributable to enantioselective presystemic conversion of MPH to RA rather than to en Anti-inflammatory excretion.

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.

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.

Kinetic analysis of enantiomers of threo-methylphenidate and its metabolite in two healthy subjects after oral administration as determined by a gas chromatographic-mass spectrometric method.

The results suggest that one reason for the difference in the plasma levels between (+)- and (-)-MPD may be due to differences in their rates of metabolism.

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.

Pharmacology of the enantiomers of threo-methylphenidate.

Results suggest that synaptic inhibition of catecholaminergic uptake by d-threo-MPH may be involved fundamentally in behavioral and pressor effects of the racemic drug.