Studies on the Metabolism of D- and L-Isomers of 3,4-Dihydroxyphenylalanine (DOPA). II. Autoradiographic Study on the Distribution of ^<14>C-Labeled D- and L-DOPA after Oral Administration in Rats

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The distribution of D- and L-^<14>C-DOPA following oral administration in rats were investigated by means of whole-body autoradiographic technique. With a constant dose level of 10 mg/kg, the distribution patterns of the two isomers were found to be significantly different from those observed after intravenous administration and almost no uptake was shown in the brain and skeletal muscle after oral administration of L-DOPA, while a prominent accumulation after that of the D-isomer. These differences were ascribed to i) a rapid metabolic change of L-DOPA in the peripheral tissues including the gastro-intestinal tract and ii) a much slower absorption of D-DOPA than L-DOPA from intestine. It was further found that the distribution pattern of L-DOPA depends on the amount of oral dose and the brain uptake was increased markedly with increasing the dose level to higher than 50 mg/kg, which is in accord with the effective dose level of L-DOPA clinically applied in the treatment of Parkinsonism. The high accumulation of D-DOPA in the tissues such as the brain and skeletal muscle and its retention for a long period might give a possible explanation for the fact found clinically that the oral use of the DL-racemate rather than the L-isomer causes a severe side effect.
社団法人日本薬学会の論文
1972-05-25