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The plasma concentration of methylphenidate (MPD) enantiomers after i.v. and oral administration of 0.5-5 mg/kg dose of racemic MPD was compared in rats. In i.v. administration, there was no dose dependence in the pharmacokinetic parameters of both enantiomers in this dose range. In oral administration, although the elimination rate constant of both enantiomers was relatively constant, the total body clearance of both MPD enantiomers decreased remarkably with increasing dose. The relationship between oral dose and the area under the concentration-time curve (AUC) of the individual MPD enantiomers showed a non-linearity. That is, the AUC of both enantiomers increased dramatically with increasing dose more than 2 mg/kg. The recovery (MPD + the metabolite) in urine for 24 h was 16-18% in the range of the oral doses. These results suggest that the dose-dependent characteristics of the MPD enantiomers may be due to the saturation in the presystemic elimination of the drug.

Dose-dependent kinetics of methylphenidate enantiomers after oral administration of racemic methylphenidate to rats.