title: Pharmacokinetics of methylphenidate after oral administration of two modified-release formulations in healthy adults.
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.
  
  
  METHODS
  Open-label, randomised, crossover, bioavailability study.
  
  
  METHODS
  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 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.
  
  
  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 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pharmaceutical Sciences, Medical University of South Carolina, Charleston, South Carolina 29425-0742, USA. markowij@musc.edu
authors.forename: John S
authors.initials: JS
authors.lastname: Markowitz
authors.forename: Arthur B
authors.initials: AB
authors.lastname: Straughn
authors.forename: Kennerly S
authors.initials: KS
authors.lastname: Patrick
authors.forename: C Lindsay
authors.initials: CL
authors.lastname: DeVane
authors.forename: Linda
authors.initials: L
authors.lastname: Pestreich
authors.forename: James
authors.initials: J
authors.lastname: Lee
authors.forename: Yanfeng
authors.initials: Y
authors.lastname: Wang
authors.forename: Rafael
authors.initials: R
authors.lastname: Muniz
mesh_terms: D000284:Administration, Oral; D000328:Adult; D019540:Area Under Curve; D001682:Biological Availability; D002214:Capsules; D000697:Central Nervous System Stimulants / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D004305:Dose-Response Relationship, Drug; D005215:Fasting; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D008774:Methylphenidate / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D013607:Tablets; D013810:Therapeutic Equivalency
chemical_list: D002214:Capsules; D000697:Central Nervous System Stimulants; D003692:Delayed-Action Preparations; D013607:Tablets; D008774:Methylphenidate