抗てんかん薬服用中患者におけるビタミンD代謝異常—生化学的検査所見および臨床因子との相関について

Disturbance of Vitamine D Metabolism in Patients Treated with Antiepileptic Drugs: Correlations with laboratory data and clinical factors

　抄録　抗てんかん薬服用中の患者54名について，vitamin D代謝異常をもたらす因子を明らかにする目的で，生化学的検査所見ならびに臨床諸因子との関係を検討した。

　血清25-hydroxyvitamin D₃（25OHD）と血清phenobarbital濃度は負の相関を示し，この薬が25OHDを不活化することが推測された。しかし，25OHDと血清diphenylhydantoinおよびcarbamazepine濃度との間には有意の相関は認められなかった。25OHD値と服薬年数との間にも有意の相関は認められなかった。一方calcium（Ca）値は25OHD値と正の相関を，服用薬剤数とは負の相関を示した。ただしCa低下の程度はhypreparathyroidismをもたらすほどではなかった。他にγ-GTPが高値を示す症例が多くみられた。

　vitamin D代謝異常は抗てんかん薬の生体への作用を基盤とし，それに個体側の因子―例えば女性，頻発する発作，精神運動発作，性格変化など患者の活動を制限し，日光暴露時間を減少させるような因子―が加わって顕在化するものと思われる。

　It is well known that the administration of antiepileptic drugs causes a disturbance of vitamin D metabilism and osteomalacia. The purpose of this study is to clarify the relationship of serum 25 hydroxyvitamin D (25OHD) to serum concentrations of antiepileptic drugs, parathyroid hormone (PTH), calcium (Ca), magnecium (Mg), inorganic phosphate (P) and clinical factors in out-patients treated with antiepileptic drugs.

　We examined 54 patients ranging in age from 15 to 60 (mean 34) and obtained the following results : 1) Abnormal values were found in terms of25 OHD (30%), Ca (37%), P (37%), Mg (30%), ALP (9%), and γ-GTP (76%), but not of PTH. This means that the degree of hypocalcemia (8.6±0.5 (S.D.) mg/ml) is not severe enough to produce secondary hyperparathyroidism.

　2) A significant inverse correlation was found between 25OHD and serum concentration of phenobarbital (p<0.025). This supports the view that this drug causes P-450 enzyme induction in the liver microsome and converts more 25OHD to inactive metabolites.

　We could not find significant correlations between 25OHD and serum concentration of diphenylhydantion, and duration of drug administration.

　3) There was a significant positive correlation between 25OHD and Ca (p <0.005). Hypocalcemia can therefore be a good indicator of reduced level of serum 25OHD. Correlations between 25OHD and other laboratory signs were not significant.

　4) High γ-GTP (79+62.6(S.D.) U.) also indicates enzyme induction in the liver microsome by drugs. This was supported by the positive correlation between γ-GTP and the number of administrated drugs (p<0.001).

　5) The disturbance of vitamin D metabolism was found more frequently in cases with such clinical factors as female sex (p <0.025), psychomotor epilepsy (p <0.005), high frequency of seizures (p<0.001) and personality changes (p <0.05). These factors may contribute in some way to the manifestation of the metabolic disturbance of vitamim D.