Lamotrigineの併用がcarbamazepineならびにcarbamazepine-10,11-epoxideの血中濃度におよぼす影響 Effect of Concurrent Administration of Lamotrigine on the Plasma Concentrations of Carbamazepine and Its Epoxide Metabolite : a Clinical Implication

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適切な抗てんかん薬物療法を行っても発作の抑制が困難で、lamotrigine (LTG) を導入したてんかん症例のうち、 LTG導入時にcarbamazepine (CBZ) を服用し、他にはLTGの代謝に影響する既知の薬物を併用していない、12~22歳 (平均18歳3カ月) の症候性ならびに潜因性局在関連性てんかん患者8例を対象に、LTG併用前後のCBZならびにcarbamazepine-10, 11-epoxide (CBZ-E) の血中濃度の変化を検討した。LTG併用時のCBZの投与量は5.8~12.0 (平均9.7±2.3) mg/kg/day、LTGの投与量は2.7~14.1 (平均7.7±3.8) mg/kg/dayであった。<BR>CBZとCBZ-Eの血中濃度は、 LTG併用前は7.91±1.07μg/mlと1.29±0.30μg/ml、併用後はそれぞれ7.78±1.33μg/mlと1.45±0.40μg/mlで、 LTG併用後CBZE血中濃度は有意 (P<0.05) に上昇した。また、血中CBZ-E/CBZ濃度比も、 LTG併用後0.16±0.03から0.18±0.03と有意 (p<0.05) に上昇した。しかし、今回の対象では、LTG併用後CBZ-E血中濃度が中毒域に達した症例はなく、臨床的にもCBZ-Eに起因する中毒症状を認めなかった。

We investigated the effect of concurrent administration of lamotrigine (LTG) on the plasma concentrations of carbamazepine (CBZ) and its pharmacologically active metabolite carbamazepine-10, 11-epoxide (CBZ-E) in patients with symptomatic or cryptogenic localization-related epilepsies whose seizures were not controlled despite adequate therapy with other prevalent antiepileptic drugs. LTG is now in experimental use in Japan.<BR>Eight study patients aged 12-22 (mean, 18 years 3 months) were first treated with CBZ, LTG was then added. Most of the patients were treated combined with other antiepileptic drugs, but they were not received those, such as phenytoin and valproic acid, which complicate the steady-state plasma concentrations of LTG as well CBZ and CBZ-E by the potential for pharmacokinetic interactions. The dosage of CBZ and other antiepileptic drugs concomitantly used was kept constant during the investigation.<BR>When the daily dosage of 7.7±3.8 mg/kg of LTG was added to CBZ therapy (9.7±2.3 mg/kg/day) in 8 patients, both plasma level of CBZ-E and plasma CBZ-E/CBZ ratio increased significantly (p<0.05) from 1.29±0.30 to 1.45±0.40, ug/ml and 0.16±0.03 to 0.18±0.03, respectively. Plasma level of CBZ remained unchanged from 7.91±1.07 to 7.78±1.33μg/ml. Plasma level of LTG was 5.91±2.29 μg/ml.<BR>It is evident that the concurrent administration of LTG affects plasma concentration of CBZ-E, while plasma CBZ level remains unaltered. Howevere, the effect of LTG on plasma concentration of CBZ-E is a little, and none of the patients showed toxic plasma concentration of CBZ-E or associated clinical toxicity.

収録刊行物

  • てんかん研究 = Journal of the Japan Epilepsy Society

    てんかん研究 = Journal of the Japan Epilepsy Society 15(1), 17-23, 1997-02-28

    一般社団法人 日本てんかん学会

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各種コード

  • NII論文ID(NAID)
    10008972454
  • NII書誌ID(NCID)
    AN10043823
  • 本文言語コード
    JPN
  • 資料種別
    ART
  • ISSN
    09120890
  • データ提供元
    CJP書誌  J-STAGE 
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