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

@article{Teo2004AST,
  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},
  year={2004},
  volume={44}
}
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.

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