小児におけるDiphenylhydantoinの血中濃度—年齢別および併用薬剤の有無による差異について

DIFFERENCE OF SERUM DIPHENYLHYDANTOIN LEVELS BETWEEN IN CASES OF TAKING DIPHENYLHYDANTOIN ALONE AND IN CASES OF TAKING MULTIPLE ANTI-CONVULSANTS IN VARIOUS AGE GROUPS

I．はじめに

　Diphenylhydantoin （以下DPH）は最も多く使用される抗痙攣剤の一つであり，臨床上，その効果の及ぶ範囲も広い。最近では，ガスクロマトグラフィー，或いはEMITの出現により，DPH血中濃度の測定が広く用いられる様になり，投与量と，その血中濃度の関係について多く論じられ^{4,13,26,27）}，現在ではdose-dependentの関係であると考えられている。

　また，DPHの血中濃度に関しては，併用薬剤により，DPHの代謝に影響を与えて，血中濃度が変化する場合があることが知られており，特にPhenobarbital （以下PB）に関しては，種々の報告がなされてきた^{2,5,6,7,16）}。

The relationship between oral dose of diphenyl-hydantoin (DPH) and serum levels of DPH in 163 epileptic children was investigated.

The serum level determination were performed by the method of Solow using gas liquid chromato-graphy.

The patients were divided into four groups ac-cording to their medication, namely, A : DPH with or without other anti-convulsants, B: DPH alone, C: DPH+phenobarbital (PB) with or without primidone (PRM), D: DPH+other anticonvulsants with or without PB (PRM).

In this study, PRM was considered equal to PB since PRM has a chemical structure similar to PB and is partly metabolized to PB.

Each groups were then subdivided into four sub-groups according to their age, 0-2, 3-5, 6-9 and over 10 years of age.

Regression lines of oral doses (mg/kg) against serum levels of DPH (μg/ml) were calculated for each respective sub-groups by the method of least squares.

Significant correlation was obtained in all sub-groups of groups A, B and C, except in the age subgroups 0-2 of groups B and C. and 3-5 of group C. The pronounced variation in the level-dose relation of DPH in the 0-2 years of age group could be explained if the mechanism of elimination were complicated and readily interfered with.

The slopes of the regression lines increased pro-gressively with age in all four groups (A, B, C and D).

Comparison among corresponding age groups revealed the slopes became steeper in the follow-ing order : group B, group C, group A.

The regression lines within corresponding age groups of groups B and D were similar, even though some cases of group D were given anti-couvulsive drugs which had been reported to raise serum levels of DPH.

Hence, under identified dosage it is speculated that the effect of PB to decrease serum levels of DPH is more intense than that of some other anti-convulsants.

The present data would suggest the interference of PB with DPH metabolism when PB is taken on a chronic basis in the cases of epilepsy.