Effects of food on the pharmacokinetics of methylphenidate

Purpose. To test the hypothesis that the pharmacokinetics of d-methylphenid ate (d-MPH) would be altered by food ingested before administration of an i mmediate release formulation (dl-MPH- IR) but not when food is ingested bef ore a slow release formulation (dl-MPH-SR). Methods. A randomized, four-phase, open label, crossover design was conduct ed in 24 healthy men who each received, on separate occasions, dl-MPH-IR an d dl-MPH-SR taken after an overnight fast and 15 min after a standardized b reakfast (20% protein, 21% fat, 59% carbohydrate). Plasma MPH levels were m onitored by a validated, stereoselective, GLC-ECD method. Results. For plasma d-MPH, there were significant differences (ANOVA) betwe en dl-MPH-IR kind dl-MPH-SR in tmax, Cmax (peak exposure), and Cmax/AUC (se nsitive 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 signifi cantly increased Cmax (23%) and AUC (15%) and for dl-MPH-SR the correspondi ng increases were Cmax (17%) and AUC (14%). After dl-MPI-I-IR, food delayed average tmax from 2.0 to 2.5 but had no effect on tmax after dl-MPH-SR. Th ere 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-MPH1R or di-M PI-I-SR.