Effects of food on the pharmacokinetics of methylphenidate.
OBJECTIVE
To test the hypothesis that the pharmacokinetics of d-methylphenidate (d-MPH) would be altered by food ingested before administration of an immediate release formulation (dl-MPH- IR) but not when food is ingested before a slow release formulation (dl-MPH-SR).


METHODS
A randomized, four-phase, open label, crossover design was conducted in 24 healthy men who each received, on separate occasions, dl-MPH-IR and dl-MPH-SR taken after an overnight fast and 15 min after a standardized breakfast (20% protein, 21% fat, 59% carbohydrate). Plasma MPH levels were monitored by a validated, stereoselective. GLC-ECD method.


RESULTS
For plasma d-MPH, there were significant differences (ANOVA) between dl-MPH-IR and dl-MPH-SR in tmax, Cmax (peak exposure), and Cmax/AUC (sensitive to rate of absorption). Dl-MPH-SR on average delayed tmax from 2.3 to 3.7 h and lowered Cmax 34%. There was no significant difference between the formulations in AUC (extent of absorption). For dl-MPH-IR, food significantly increased Cmax (23%) and AUC (15%) and for dl-MPH-SR the corresponding increases were Cmax (17%) and AUC (14%). After dl-MPH-IR, food delayed average tmax from 2.0 to 2.5 but had no effect on tmax after dl-MPH-SR. There was no effect of food on Cmax/AUC (rate of absorption).


CONCLUSIONS
Food caused a significant increase in extent of absorption but had no effect on rate of absorption of d-MPH after either dl-MPHIR or dl-MPH-SR.
Midha
K K
KK
PharmaLytics Inc, Saskatoon, SK, Canada.
McKay
G
G
Rawson
M J
MJ
Korchinski
E D
ED
Hubbard
J W
JW
D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002849:Chromatography, Gas; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D004563:Electrochemistry; D005260:Female; D018565:Food-Drug Interactions; D006801:Humans; D008297:Male; D008774:Methylphenidate / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008875:Middle Aged; D013237:Stereoisomerism
D000697:Central Nervous System Stimulants; D003692:Delayed-Action Preparations; D008774:Methylphenidate