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.

Abstract

The effect of a high-fat meal on the pharmacokinetics of OROS(R) (methylphenidate HCl), an osmotic controlled-release formulation of methylphenidate HCl, was investigated in healthy subjects. Mean peak methylphenidate plasma concentrations occurred slightly later and peak methylphenidate plasma concentrations and AUC values were slightly higher (approximately 10-30%) in the presence of food than in the absence of food. There was no difference in the plasma elimination half-life of methylphenidate between the fed and fasted state. Similarly, peak concentrations and AUC values for alpha-phenyl-2-piperidine acetic acid (PPA; ritalinic acid), the major metabolite of methylphenidate, were slightly higher in the presence of food than in its absence. The 90% confidence interval (CI) for the treatment ratio (fed/fasted) for C(max) was 120.6%-140. 0% for the 18-mg dose and 105.4-119.3% for a 36-mg dose. The 90% CI for the treatment ratio for AUC(infinity) was 114.6-125.7% for the 18-mg dose and 115.1-124.6% for the 36-mg dose. PPA levels were measured following the 18-mg dose and the 90% CI of the treatment ratio was 106.8-115.4% for C(max) and 97.9-103.6% for AUC(infinity). These results indicate the absence of dose dumping from OROS (methylphenidate HCl) in the presence of food. Food does not impede drug absorption and OROS (methylphenidate HCl) may be administered in the fed or fasted state. There were no differences in the adverse event profile between the fed and fasted state.