title: Sex differences in the kinetic profiles of d- and l- methylphenidate in the brains of adult rats.
abstract: OBJECTIVE
  Methylphenidate is commonly used in the treatment of Attention Deficit Hyperactivity Disorder and narcolepsy. Methylphenidate is administered as a racemic mixture of the d- and l- threo enantiomers; however, the d-enantiomer is primarily responsible for the pharmacologic activity. Previous studies of the behavioral effects of methylphenidate have highlighted sex differences in the responsiveness to the drug, namely an increased sensitivity of females to its stimulatory effects. These differences may be due to differences in the uptake, distribution, and elimination of methylphenidate from male and female brains. Therefore, we compared the pharmacokinetics of d- and l- threo methylphenidate in the brains of male and female rats.
  
  
  METHODS
  Adult male and female Sprague-Dawley rats were injected with 5 mg/kg d, l- threo methylphenidate, and whole brains were collected at various time points following injection. We measured methylphenidate concentrations utilizing chiral high pressure liquid chromatography followed by mass spectrometry.
  
  
  RESULTS
  Females exhibited consistently higher brain concentrations of both d- and l- methylphenidate and a slower clearance of methylphenidate from brain as compared to males, particularly with the active d-enantiomer.
  
  
  CONCLUSIONS
  The increased sensitivity of females to methylphenidate may be partially explained by an increase in total brain exposure to the drug.
authors.affiliation: Department of Pharmaceutical Sciences, Bill Gatton College of Pharmacy, East Tennessee State University, Johnson City, TN, USA. pond@etsu.edu.
authors.forename: J
authors.initials: J
authors.lastname: Bentley
authors.forename: F
authors.initials: F
authors.lastname: Snyder
authors.forename: S D
authors.initials: SD
authors.lastname: Brown
authors.forename: R W
authors.initials: RW
authors.lastname: Brown
authors.forename: B B
authors.initials: BB
authors.lastname: Pond
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D005260:Female; D008297:Male; D008774:Methylphenidate / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012727:Sex Characteristics; D013237:Stereoisomerism
chemical_list: D008774:Methylphenidate