Toxicokinetic assessment of methylphenidate (Ritalin) in a 13-week oral toxicity study in dogs.
Tools
Tools
Bakhtiar, Ray, Ramos, Luis and Tse, Francis (2004) Toxicokinetic assessment of methylphenidate (Ritalin) in a 13-week oral toxicity study in dogs. Biomedical Chromatography, 18 (1). pp. 45-50. ISSN 0269-3879
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 1-2 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.
| Item Type: | Article |
|---|---|
| Related URLs: | |
| Additional Information: | archiving not allowed on institutional repository |
| Keywords: | mass spectrometry; Ritalin; toxicokinetic; enantioselective; atmospheric pressure chemical ionization; dogs; vancomycin column |
| Related URLs: | |
| Date Deposited: | 14 Dec 2009 14:01 |
| Last Modified: | 31 Jan 2013 01:19 |
| URI: | https://oak.novartis.com/id/eprint/329 |