Toxicokinetic assessment of methylphenidate (Ritalin) enantiomers in pregnant rats and rabbits.
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Bakhtiar, Ray and Tse, Francis (2004) Toxicokinetic assessment of methylphenidate (Ritalin) enantiomers in pregnant rats and rabbits. Biomedical chromatography : BMC, 18 (5). pp. 275-281. ISSN 0269-3879
Abstract
Ritalin or methylphenidate (MPH) is prescribed for the treatment of attention deficit hyperactivity disorder (ADHD) and narcolepsy. The present report describes the determination of plasma concentrations of D-threo- and L-threo-enantiomers of MPH in toxicokinetic (TK) studies in pregnant Wistar Hannover rats and New Zealand white rabbits following repeated daily oral dosing of D,L-MPH (racemate). A previously reported chiral liquid chromatography tandem mass spectrometric (LC-MS/MS) method with a lower limit of quantification (LLOQ) of 1.09 ng/mL was utilized. Oral (gavage) doses of 7, 25 and 75 mg/kg/day of racemic MPH were selected for the rat study. An over-proportional increase in exposure was observed with increasing doses of MPH racemate, the effect being more profound with the D- than the L-enantiomer. In contrast, Cmax values of both enantiomers were approximately proportional to the dose. Oral (gavage) doses of 20, 60 and 200 mg/kg were selected for the rabbit study. In general, for the D-isomer, an over-proportional increase in exposure was observed with increasing doses of MPH racemate. Conversely, for the L-isomer, a slight under-proportionality was detected in exposure with increasing doses of D,L-MPH. For mean Cmax, while L-isomer exhibited dose proportionality with increasing doses of MPH racemate, the D-isomer appeared to be over-proportional. Herein, the experimental design and observed TK parameters in each study are presented.
| Item Type: | Article |
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| Additional Information: | Not allowed on institutional repository |
| Keywords: | mass spectrometry; Ritalin®; toxicokinetic; enantioselective; atmospheric pressure chemical ionization; methylphenidate; vancomycin column |
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| Date Deposited: | 14 Dec 2009 14:07 |
| Last Modified: | 31 Jan 2013 01:31 |
| URI: | https://oak.novartis.com/id/eprint/50 |