A single-dose, two-way crossover, bioequivalence study of dexmethylphenidate HCl with and without food in healthy subjects.
J Clin Pharmacol
; 44(2): 173-8, 2004 Feb.
Article
en En
| MEDLINE
| ID: mdl-14747426
ABSTRACT
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 x 10-mg tablets), two-way crossover with d-MPH administered to subjects in both a fasting state or after a high-fat breakfast. There were no serious or unexpected adverse events during the course of this study, with most events reported in comparable numbers of fed and fasted subjects. The bioequivalence of d-MPH was similar with or without food, with 90% confidence intervals of 88.2% to 104.6% and 105.9% to 118.2% for ln(C(max)) and ln[(AUC(0-infinity))], respectively. There was a marginal but statistically significant 1-hour increase in t(max) in the fed versus fasted state, reflecting an absorption delay. The rate of formation of the major metabolite, d-ritalinic acid (d-RA), was marginally decreased ( approximately 14%) after food. The extent of exposure to d-RA was similar (within 1.2%) between both treatments. There was a marginal but statistically significant difference in mean t(max) for d-RA between fed and fasted conditions, with peak concentration occurring 1.5 hours later after d-MPH administration with food. There was no measurable in vivo chiral inversion of d-MPH to l-MPH in plasma. In addition, the metabolism of d-MPH was stereospecific as d-MPH only produced d-RA. In summary, food had no substantial effect on the bioavailability of d-MPH, with an equivalent rate and extent of exposure obtained. Therefore, d-MPH can be administered without regard to food intake.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Interacciones Alimento-Droga
/
Clorhidrato de Dexmetilfenidato
/
Estimulantes del Sistema Nervioso Central
/
Metilfenidato
Tipo de estudio:
Clinical_trials
/
Prognostic_studies
Límite:
Adult
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
J Clin Pharmacol
Año:
2004
Tipo del documento:
Article
País de afiliación:
Estados Unidos