Pharmacokinetics of methylphenidate after oral administration of two modified-release formulations in healthy adults

• Published in: Clinical pharmacokinetics Vol. 42; no. 4; pp. 393 - 401
• Main Authors: MARKOWITZ, John S, STRAUGHN, Arthur B, PATRICK, Kennerly S, DEVANE, C. Lindsay, PESTREICH, Linda, LEE, James, YANFENG WANG, MUNIZ, Rafael
• Format: Journal Article
• Language: English
• Published: Auckland Adis international 2003
• Subjects: Administration, Oral; Adult; Area Under Curve; Biological and medical sciences; Biological Availability; Capsules; Central Nervous System Stimulants - administration & dosage; Central Nervous System Stimulants - blood; Central Nervous System Stimulants - pharmacokinetics; Cross-Over Studies; Delayed-Action Preparations; Dose-Response Relationship, Drug; Fasting; Female; Half-Life; Humans; Male; Medical sciences; Methylphenidate - administration & dosage; Methylphenidate - blood; Methylphenidate - pharmacokinetics; Neuropharmacology; Pharmacology. Drug treatments; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; Tablets; Therapeutic Equivalency; Human; Healthy subject; CNS stimulant; Psychotropic; Oral administration; Dosage form; Capsule; Tablet; Bioavailability; Pharmacokinetics; Comparative study; Methylphenidate
• ISSN: 0312-5963
• DOI: 10.2165/00003088-200342040-00007

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. Open-label, randomised, crossover, bioavailability study. Twenty healthy adult male and female volunteers. Subjects received single doses of two modified-release formulations of MPH, a 20mg capsule (Ritalin) LA) and an 18 mg 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. 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 microg/L at an average of 2.1 hours after administration and a second peak of 9.3 microg/L occurring at 5.6 hours. In contrast, the profile of the Concerta formulation rapidly reached an initial plateau concentration of 3.4 microg/L at 3.3 hours after administration and a second mean plateau concentration of 5.9 microg/L approximately 6 hours after administration. Substantially more MPH was absorbed from Ritalin LA than from Concert over the first 4 hours; the respective AUC(4) values were 18.5 and 9.3 microg x 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. 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 20 mg capsule formulation provides more rapid absorption and higher peak plasma concentrations than the recommended 18 mg starting dose of the Concerta formulation.