Kinetic analysis of enantiomers of threo-methylphenidate and its metabolite in two healthy subjects after oral administration as determined by a gas chromatographic-mass spectrometric method.
A gas chromatographic-mass spectrometric method was developed for the stereoselective quantification of threo-methylphenidate (MPD) and its metabolite, ritalinic acid (RA), in plasma or urine. The plasma concentrations of (+)-MPD after oral administration of two 10-mg conventional tablets containing racemic MPD.HCl or of 20-mg of racemic MPD.HCl crystals to two healthy subjects were much higher than those of the (-)-isomer. The plasma concentrations of the metabolite, (-)-RA, were higher than that of the (+)-isomer during the first 4 h after administration of racemic MPD.HCl in both tablet and crystal forms. Although in urine both (+)- and (-)-RA were largely excreted in 48 h (37 and 40% of the dose, respectively), the percentage excretion of (-)-RA during the first 3-4 h was approximately twice that of the (+)-isomer. These results suggest that one reason for the difference in the plasma levels between (+)- and (-)-MPD may be due to differences in their rates of metabolism. Pharmacokinetic parameters of (+)-MPD after administration of 10 mg of (+)-MPD.HCl crystals were almost the same as those after administration of racemic MPD.HCl crystals. The AUC infinity 0 of (-)-MPD after administration of 10 mg of (-)-MPD.HCl crystals was smaller than that after administration of racemic MPD.HCl crystals.
Aoyama
T
T
Hospital Pharmacy, Faculty of Medicine, University of Tokyo, Japan.
Kotaki
H
H
Honda
Y
Y
Nakagawa
F
F
D000284:Administration, Oral; D000328:Adult; D008401:Gas Chromatography-Mass Spectrometry; D006207:Half-Life; D006801:Humans; D007202:Indicators and Reagents; D008297:Male; D008774:Methylphenidate / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D012016:Reference Values; D013237:Stereoisomerism
D007202:Indicators and Reagents; D008774:Methylphenidate; C009189:ritalinic acid