リファンピシンの相互作用により塩酸ピルジカイニド，燐酸ジソピラミド，ワルファリンの効果が消失ないし減弱した心房細動の1例

A Case of Drug Interaction with Rifampicin Inducing Reduced Therapeutic Activity of Pilsicainide Hydrochloride, Disopyramide Phosphate and Warfarin Potassium during Treatment of Atrial Fibrillation

　症例は56歳，男性．結核性胸膜炎にてリファンピシン（RFP）450mg／dayを投与中であった．慢性心房細動（Af）に対しワルファリン（Wa）投与下に直流除細動（DCC）を施行，洞調律化後に燐酸ジソピラミド300mg／dayを開始したが，Afが再発した．21日後の血中濃度は感度以下で本剤を中止した．再度DCC施行し洞調律後に塩酸ピルジカイニド150mg／dayに変更したが，Afが再発した．14日後の血中濃度は感度以下で，本剤を中止した．その後，胸膜炎は著明に改善し，RFPの投与を終了した．Wa投与下にDCCを施行し，洞調律後に塩酸ピルジカイニド150mg／dayを再開した．以後6カ月間以上洞調律は維持され，血中濃度はすべて治療域に入り，コントロール不良であったトロンボテストも改善した．

　RFPは肝のチトクロームP450酵素を誘導し，多くの薬剤の代謝速度を速めることが知られている．本例のように同一症例で3剤抑制や，塩酸ピルジカイニドとの相互作用報告はなく報告した．

A 58-year-old man treated with rifampicin 450mg daily was admitted to our hospital for treatment of atrial fibrillation. After reversion to sinus rhythm by direct current cardioversion ＜DCC＞ with warfarisation, disopyramide 300 mg daily was prescribed. After relapse of atrial fibrillation, the disopyramide serum level was shown to be under 0.3μg/ml, which is below the suggested therapeutic range of 2 to 5μg/ml. After the second DCC, pilsicainide was prescribed. After a further relapse, the pilsicainide serum level was under 0.05μg/ml, which is below the suggested therapeutic range of 0.2 to 1.0μg/ml, and the thrombotest was 120% under wafarin 6mg per day. After discontinuation of rifampicin and a third cardioversion, the pilsicainide serum levels were between 0.33 and 0.54μg/ml, sinus rhythm could be maintained, and the thrombotest could be stabilized within the required therapeutic range with a warfarin daily dose of 3 mg.

We have observed extremely low pilsicainide and disopyramide serum concentration and high throm-botest levels during concomitant treatment with rifampicin.

The results suggest that rifampicin is able to induce cytochrome P 450 enzymes in the liver and to reduce the therapeutic effect of these three drugs.