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- Title
Toxicokinetic assessment of methylphenidate (Ritalin<sup>®</sup>) in a 13-week oral toxicity study in dogs.
- Authors
Ray Bakhtiar; Luis Ramos; Francis L. S. Tse
- Abstract
Ritalin® or methylphenidate (MPH) is often prescribed for the treatment of attention deficit hyperactivity disorder (ADHD) and narcolepsy. The therapeutic activity of MPH is principally due to d-threo-[2R,2'R]-MPH. Hence, in order to establish a kinetic relationship between doses and exposure levels in a non-rodent species, a 13-week oral (capsule) toxicity study of d-threo-[2R,2'R]-MPH was performed in beagle dogs. A previously reported chiral liquid chromatography tandem mass spectrometry (LC-MS/MS) with a limit of quantification (LLOQ) of 1.09 ng/ml was utilized. The results of this study indicated that MPH appeared to be rapidly absorbed in dogs following oral administration. The peak concentration was reached within 12 h. Based on the area under the curve (AUC) values, the plasma exposure of d-MPH was over-proportional to the dose. With the exception of two groups of animals (male/female, 7.5 mg/kg/day on day 1 and male/female, 3.0 mg/kg/day on week 7), the data showed no difference in MPH concentrations between the male and female dogs. Taking the statistical variations into account, concentrations of d-MPH that were observed after 7.5 mg/kg/day doses of d-MPH and 15 mg/kg/day doses of the racemate were similar. Following the racemate doses, the concentrations of l-MPH were consistently higher than those of the d-isomer. No accumulation of MPH was observed after 13 weeks of repeated daily administration. Copyright © 2003 John Wiley & Sons, Ltd.
- Subjects
METHYLPHENIDATE; PIPERIDINE; TREATMENT of attention-deficit hyperactivity disorder; NARCOLEPSY; LIQUID chromatography; DRUGS; THERAPEUTICS
- Publication
Biomedical Chromatography, 2004, Vol 18, Issue 1, p45
- ISSN
0269-3879
- Publication type
Article
- DOI
10.1002/bmc.290