Carbamazepine血清内濃度の服薬期間依存性について

TIME-DEPENDENCY OF SERUM CARBAMAZEPINE CONCENTRATION

Ⅰ．はじめに

　Carbamazepine （CBZ）はてんかん発作，とりわけ精神運動発作と大発作に効果を発揮するといわれている。1976年に福島^11）が日本てんかん研究会会員からアンケート調査によつて得た結果によると回答者全員がCBZを使用していた。この事実からも本剤の臨床面における必要度がきわめて高いことが推し量られるであろう。

　かくのごとく臨床の実際面で広く賞用されているわりには，CBZの生物学的利用率および薬物動力学に関する知識には不明な点が多い。

The authors had investigated correlation between serum carbamazepine (CBZ) concentration and its dose in epileptic patients, and had found that CBZ of large dose did not necessarily show high serum concentration. In the subsequent study, we had found 5 cases in which serum CBZ concentration fell down after the transient elevation in the first several weeks of CBZ treatment. From these results, we assumed that CBZ metabolism varies in the course of the treatment.

Accordingly, in the present study, we tried to confirm whether the length of period of CBZ treatment gives some influence on serum CBZ concentration or not, with reference to differences between children and adults.

Serum CBZ concentration was determined by the gas liquid chromatographic method in 22 epileptic patients (88 samples) treated from the outset with CBZ alone, and the following results were obtained.

1. As the treatment was continued, serum CBZconcentration, at first, rose rapidly within the end of about 10 days after initiation of CBZ adminis-tration, and thereafter, rate of increase of the con-centration was gradually decreased.

2. The relation between duration of the treatment and serum concentration/dose ratio was expressed by a regression curve, representing a quardatic function with negative coefficient. This regression curve showed that the ratio had the peak at the 10.7th day from the outset of the treatment. The ratio was stabilized, with scatters, at lower level after the 3-4 weeks of the CBZ administration.

3. From the above mentioned results, and the measurement of time-course change in serum con-centration in 3 administerated cases of the present study, serum CBZ concentration was confirmed to be more depent on period of the treatment than on dose, and the phenomena was inferred to be attributable to the autoinduction of CBZ metabo-lism.

4. The serum CBZ concentration of 4 cases with or without other antiepileptic drugs varies greatly within 12hr.

5. The rate of CBZ metabolism would be more rapid in child epileptic patients than in adults.

6. On the basis of these results, it is proposed that spontaneous decrease in serum CBZ concen-tration must be counteracted not merely by increase in CBZ dose, but by increase in the number of dosages/day for suppression of excessive diurnal change in serum concentration as well.