L-DopaのSuperenteric coating錠—その吸収，排泄および臨床効果の検討

ABSORPTION, EXCRETION, AND CLINICAL EFFECTS OF L-DOPA PREPARATION WITH SUPERENTERIC COATING IN PARKINSONISM

I．はじめに

　L-DopaがParkinsonismの治療に有効であることは広く認められ，既に臨床的に多数の症例に対して用いられている。しかし，L-Dopa投与の副作用として，悪心，嘔吐などの胃腸症状が出現し，治療上の妨げになる例も少なくない。このような副作用に対して，L-DopaにMK-486などのdecarboxylase inhibitorを併用しL-Dopaの投与量を少なくすることも一つの試みであろう。

　一方，従来のL-Dopa製剤は胃溶性であるため，経口投与後，胃で溶解し，直接胃壁に作用して副作用の出現に一部関与しているものと思われる。そこでL-Dopa製剤が胃で崩壊せず，小腸ではじめて溶解し吸収されるように作られれば，胃腸症状の出現を防ぎうる可能性がある。しかし，L-Dopaの腸溶剤に関する従来の報告をみると，L-Dopaの吸収が極めて不充分であつたため，臨床的に実用化されるには至つていない^3,9）。

The absorption, excretion, and clinical effects of L-Dopa and its metabolites were compared between the new preparation with Superenteric coating capsules (S. E. preparation) and conventional prepa-ration after oral administration to 5 patients with Parkinsonism. The Superenteric coating capsules were so prepared that they never resolve until they arrive at the upper intestine where they resolve completely within 10 minutes.

There was no significant difference between these two preparations in the peak concentration and the rate of recovery in the urine. The cumulative areas of plasma L-Dopa and the amount of L-Dopa which entered a unit volume of distribution be-tween time 0 and 6 hours were greater in S. E. preparation than in conventional preparation. These results indicate that absorption rate of the new preparation is equal to, or slightly higher than, the previous conventional L-Dopa preparation.

Plasma concentration of L-Dopa and dopamine rised more gradually and sustained relatively high values for longer time in S. E. preparation than in conventional preparation. The difference of plasma L-Dopa concentration 6 hours after oral adminis-tration between these two preparations was signifi-cant.

In 2 of 5 cases Parkinsonian symptoms improved more significantly with S. E. preparation than with conventional preparation. Nausea and vomiting were less frequent in the new preparation.

It was concluded that S. E. preparation of L-Dopa is slightly more useful than conventional prepa-ration.