Abstract

Objectives: Primary objective was to investigate bioequivalence of Ritalin LA^® 40 mg compared to Medikinet^® retard 40 mg in healthy male volunteers under fasted and fed conditions. Secondary objectives included assessment of tolerability and determination of further pharmacokinetic parameters. The difference between the kinetic profiles of Ritalin LA^® and Medikinet^® retard with respect to breakfast intake was additionally explored. Methods: 28 subjects were randomized in this open-label, four-treatment, cross-over-design study. Pharmacokinetic evaluations included AUC_(0-inf), C_max, t_max, elimination half life (t_1/2) and mean residence time (MRT_(0-inf)). The relative bioavailability of Ritalin LA^® and Medikinet^® retard and the food effect were assessed using a 90% confidence interval (CI) based on the lower and upper endpoints of the CI for the ratios of the geometric means being within the 80 – 125% equivalence criterion. Results: 25 volunteers completed all treatment arms. Frequency of adverse events were comparable for all treatments. Under fasted condition Ritalin LA^® showed a consistent bimodal concentration time profile with two t_max peaks. Medikinet^® retard showed a steady absorption with a single t_max peak. The point estimators for AUC_(0-inf) and C_max were found to be 99.7% and 85.9%, respectively. Under fed condition both Ritalin LA^® and Medikinet^® retard showed a bimodal concentration time profile with two tmax peaks. The point estimators for AUC_(0-inf) and C_max were estimated as 89.8% and 68.6%, respectively. Conclusions: Both methylphenidate formulations were safe and well tolerated. Ritalin LA^® and Medikinet^® retard were bioequivalent in fasted state but not in fed state. Only Ritalin LA^® had a biphasic kinetic profile under both fasted and fed conditions. This difference in the kinetic profiles might be of clinical relevance and might offer a potential advantage of Ritalin LA^®.

Author Details

Authors

• F. Haessler¹
• F. Tracik²
• H. Dietrich³
• H. Stammer⁴
• J. Klatt²

Departments

• ¹ Clinic for Child Psychiatry, Neurology, Psychosomatics and Psychotherapy, University Hospital Rostock,
• ² Novartis Pharma GmbH, Nuremberg,
• ³ ClinPharmCologne, MEDA Manufacturing GmbH, Cologne, and
• ⁴ Pharmalog Institut für klinische Forschung GmbH, Munich, Germany

Address

Dr. med. J. Klatt; Novartis Pharma GmbH, Roonstraße 25, 90429 Nürnberg, Germany
Email: [email protected]

Citation