Toxicokinetic assessment of methylphenidate (Ritalin) enantiomers in pregnant rats and rabbits

Biomedical Chromatography : BMC
Ray Bakhtiar, F Tse

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 Cma...Continue Reading

Citations

May 27, 2011·Neuroscience Bulletin·Normand Carrey, Michael Wilkinson
Feb 16, 2010·Journal of Addictive Diseases·James A InciardiMark W Parrino
Oct 17, 2008·Birth Defects Research. Part B, Developmental and Reproductive Toxicology·David A BeckmanFrancis L S Tse
Oct 31, 2014·Biomedical Chromatography : BMC·R Nageswara Rao, K Guru Prasad
Dec 19, 2014·The International Journal of Neuropsychopharmacology·François-Xavier LepelletierLaurent Galineau
Jan 15, 2008·Birth Defects Research. Part B, Developmental and Reproductive Toxicology·David A BeckmanFrancis L S Tse
Aug 30, 2005·Birth Defects Research. Part B, Developmental and Reproductive Toxicology·Mari GolubMary Vore

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