Pharmacokinetics of Methylphenidate After Oral Administration of Two Modified-Release Formulations in Healthy Adults

Publisher Website
Google Scholar
Abstract
Objective: To compare the rate and extent of absorption of DL-threo-methylphenidate (MPH) from two modified-release MPH formulations at their respective recommended starting doses in healthy adult volunteers. Design: Open-label, randomised, crossover, bioavailability study. Participants: Twenty healthy adult male and female volunteers. Methods: Subjects received single doses of two modified-release formulations of MPH, a 20mg capsule (Ritalin® LA) and an 18mg tablet (Concerta®). A total of 19 plasma samples was collected over 24 hours, and MPH plasma concentrations were determined by liquid chromatography-mass spectrometry (LC-MS/MS). These values were used to calculate standard noncompartmental pharmacokinetic parameters describing the rate (peak concentration and time to peak concentration) and extent (area under the concentration-time curve, AUC) of absorption of the two formulations. The relative bioavailability of the two drugs was assessed using a 90% confidence interval, based on the lower and upper endpoints of the confidence interval for the ratios of the geometric means (log transformed) being within the 0.80–1.25 equivalence criterion. Results: Nineteen subjects, ten male and nine female, aged 21–34 years completed both treatment phases of the study. The Ritalin® LA formulation displayed a distinctly biphasic pharmacokinetic profile, with mean initial peak plasma concentration of 7 µg/L at an average of 2.1 hours after administration and a second peak of 9.3 µg/L occurring at 5.6 hours. In contrast, the profile of the Concerta® formulation rapidly reached an initial plateau concentration of 3.4 µg/L at 3.3 hours after administration and a second mean plateau concentration of 5.9 µg/L approximately 6 hours after administration. Substantially more MPH was absorbed from Ritalin® LA than from Concerta® over the first 4 hours; the respective AUC4 values were 18.5 and 9.3 µg · h/L (p < 0.001). The overall extent of absorption of MPH was similar between the two formulations. Oral clearance was identical between the two dosage forms. Conclusion: The Ritalin® LA formulation exhibited more rapid initial absorption and reached significantly higher peak plasma concentrations compared with the Concerta® formulation, although the oral bioavailability of MPH was similar between the two formulations. The Ritalin® LA capsule demonstrated a distinctly bimodal plasma concentration-time profile. MPH plasma concentrations resulting from Concerta® reached a peak at 6 hours. These results indicate that the recommended starting dose of the Ritalin® LA 20mg capsule formulation provides more rapid absorption and higher peak plasma concentrations than the recommended 18mg starting dose of the Concerta® formulation.