Effect of food on the pharmacokinetics of osmotic controlled-release methylphenidate HCl in healthy subjects

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.

Pharmacokinetic Variability of Long-Acting Stimulants in the Treatment of Children and Adults with Attention-Deficit Hyperactivity Disorder

“…This finding was similar to a previous study that found differences of 10-30% for AUC values between the fasted and fed states with Concerta Ò . [73] Also, although not reaching statistical significance, a mean prolongation in T max values of 1.9 and 2.6 hours was observed for the fed (vs fasted) states of Concerta Ò and Adderall XR Ò , respectively. [72] Beaded technologies appear particularly susceptible to pharmacokinetic changes associated with food, whereas the extent of absorption of methylphenidate from the wax-based matrix of Ritalin SR Ò appears to be modestly enhanced when administered with food.…”

Bioequivalence of Sandoz methylphenidate osmotic‐controlled release tablet with Concerta® (Janssen‐Cilag)

“…The remaining profiles show a continuous increase, which means that drug release from the immediate-release and extended-release phase overlap and cannot be separated by a cut-off; hence the immediate-release and the extended-release phase cannot be adequately characterized using partial pharmacokinetic parameters under fed conditions (Modi et al. 2000 ). The two different types of profiles (biphasic or continuous) under fed conditions are most likely caused by differences in the first site of deposition of the dosage form within the stomach directly after ingestion.…”

Sustained release methylphenidate for the treatment of ADHD in amphetamine abusers: A pilot study

“…The OROS MPH HCl delivery system contains a drug overcoat of IR MPH (consisting of 22% of the active substance) designed to dissolve shortly after swallowing the capsule, resulting in an initial rapid increase in plasma concentration, and an osmotic release system which provides a gradual increase in plasma concentration that peaks approximately 6 to 8 hours after dosing. The plasma concentration then gradually declines, reaching the baseline values by 24 hours (Modi NB, 2000).…”