Interaction in Tissue Distribution between Methylphenidate and Pemoline. I. : Tissue Distribution of Methylphenidate and Its Metabolite in the Rat

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Plasma, blood and tissue concentrations of methylphenidate (MPD) and its metabolite, ritalinic acid (RA), were measured after intravenous administration of MPD and RA to rats. After administration of 1 mg/kg dose of MPD, concentrations of MPD in the kidney, lung, brain and liver were remarkably higher than that in plasma. The concentration of RA in the brain was quite low. The mean blood-to-plasma concentration ratios of MPD and RA were 1.13 and 0.884,respectively, while, the mean ratio of RA after administration of 1 mg/kg of RA was 0.895. This finding indicates that the presence of MPD did not affect the blood-to-plasma concentration ratio of RA. After the RA administration, although the highest concentration of RA was found in the kidney, the concentration was only 3-fold that in plasma. From the results of distribution of MPD and RA, and of in vitro hydrolysis of MPD in tissues, it was suggested that MPD was hydrolyzed in all tissues examined, and also that the small amounts of RA found in the brain after MPD administration represent the results of nonenzymatic and enzymatic hydrolyses of MPD, and the direct distribution of RA. A two-compartment open model was able to fit the plasma data of MPD and RA after administration of MPD and RA, respectivery. The elimination rate constant (β), steady-state volume of distribution (V_<ss>) and total body clearance (Cl) of MPD were approximately 2,6 and 10 times larger than those of RA, respectively.
社団法人日本薬学会の論文
1988-08-25

Interaction in Tissue Distribution between Methylphenidate and Pemoline. I. : Tissue Distribution of Methylphenidate and Its Metabolite in the Rat

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