Dipropylacetic acid sodium （Depakene）の血中レベルと臨床

CLINICAL STUDY OF SERUM LEVEL OF DIPROPYLACETIC ACID SODIUM (DEPAKENE) BY GASCHROMATOGRAPHY

I．はじめに

　抗てんかん剤の血中レベルの測定は，すでに多くの施設で試みられ，いろいろの薬剤について，少なからざる報告がみられる。むしろ現在では，血中レベルの測定と臨床との相関について，今後どのような有用性が求められるか，再吟味を要求されてきているともいえよう。個々の薬剤の血中レベルの動向については，臨床薬理学上，大体一定の結果が確立されつつある^9）。しかし他剤同時服用の場合，その結果はまちまちであり，いわゆるpolypharmacyの問題をめぐつて，今後も報告が増加するであろう。既に以前からphenobarbital （以下PBと略）と，diphenylhydantoin （DPH）との相互干渉は問題にされてきた^1,3）。

　最近各方面でかなり使用されるようになつたDipro—pylacetic acid sodium （DPAと略）はフランスで開発され^7），今では欠神発作等に対する第一選択の薬剤であるといわれている。本剤は直鎖系の低級肪脂酸でその構造式は第1図の通りである。本剤の血中レベルの動向については，すでにLoiseau et al^6），武田ら^11）の報告がみられるが，まだ充分確立された所見に乏しい。また投与方法，薬量，測定時期，対象患者の質などにも各施設で相違があると考えられるので，われわれの結果をここに報告しておきたい。またDPAについても，PBやその他の薬剤との血中レベル上での相互干渉がみられるようであり^11），臨床治療上問題となるので，この面にも若干触れてみたい。

The serum level of dipropylacetic acid sodium (Depakene) was investigated in the cases of 49 epileptic patients by gaschromatography. At the same time, diphenylhydantoin (DPH), phenobarbital (PB), and carbamazepine (CBZ) were examined in the same samples of those subjects.

The blood was drawn twice in the different morning times in each patient 3-4 hours later after taking medicine.

The subjects were divided in 4 groups. The group-Ⅰ of 8 cases was administered the single dose of dipropylacetic acid sodium (DPA). The group-Ⅱ of 10 cases took the PB and other drugs in addi-tion to DPA. The group-Ⅲ of 8 cases took the primidone (PM) furthermore in addition to the drugs of group-Ⅱ. The group-Ⅳ of the rest subjects was not mentioned here because of the special stress point of the interaction of DPA, PB and PM. Furthermore, the main aims of the investigation were to get some information about the serum level of DPA as a single dose and to know the DPA distribution in serum in the case of polypharmacy.

The mean serum concentration of DPA in group-I was 68.57±27.81μg/ml at the dose of mean 12.25 ±3.34mg/kg. Between the dose and the serum concentration of DPA there was statistically linear correlation (r=0.77). The level:dose ratio showed also a significant correlation (r=0.50). Clinically, the cases among the 8 of group-Ⅰ had a good pro-gress in clinical seizure control; 3 excellently, and 4 moderately.

By contraries of the results of group-Ⅰ, the group-Ⅱ and -Ⅲ did not show uniformly applied correla-tion between the dose and serum level of DPA and PB respectively. On the other hand, there was not found a significant change of serum level of DPA under relatively high PB concentration (39.20 ± 26.70μg/ml) of the group-Ⅱ.

As mentioned above, the polypharmacy including the DPA revealed an intricate problem in serum concentration level about each drug. It was em-phasized that a more careful administration of the drugs must be needed in future.