難治性心不全例に対する新強心薬TA−064の効果の検討—初回投与時と1カ月後の血行動態指標を中心に

Acute and sustained hemodynamic effects of a new inotropic agent TA-064(Denopamine) in patients with refractory heart failure with special reference to dose-response effects

　ジギタリスがW．Witheringにより臨床に導入されてからすでに200年余を経過したが，いまだにこれを超える強心薬は出現していない。一方，従来からの利尿剤を含めた心不全治療に加えて，血管拡張薬による減負荷療法やカテコールアミンの使用，さらにECUM（Extra—corporial ultrafiltration method）やIABP （Intra aortic　balloon pamping）など補助循環が急性期を含めた心不全の治療体系に取り入れられるようになった。このため心不全の治療法が改善され，急性期を脱した重症例を長期にわたりどのように心不全を管理したらよいかが今後一層問題になると考えられる。またカテコールアミンの持続点滴からの離脱が困難な例に遭遇する機会も増えてきている。このような状況下で，治療域が狭く，重篤な不整脈をおこす可能性をもったジギタリスに代わりうる，あるいはジギタリスとの併用が可能な新たな経口強心薬の出現が期待される。近年，従来の治療に抵抗を示す重症心不全例に対して，新しく開発された経口強心薬が有効との報告^1〜6）が多くなされつつある。そのなかで我国で開発されたTA−064，（−）-（R）-1-（P-hydroxyphenyl）—2-〔（3,4-dimethoxyphenethyl） amino〕ethanol（denopa—mine）を難治性心不全患者に使用し，初回投与時と連用投与1カ月後の2度にわたり観血的方法を用いて血行動態指標を中心にその強心効果を検討したので報告する。

In recent years there have been reports on the effects of new oral cardiotonic agents in cases of severe heart failure resistant to conventional therapy. One of these new drug is TA-064 (Denopamine), hydroxybenzyl alcohol derivative.

We administered this drug orally (20 mg and/or 40 mg) to 18 patients with refractory heart failure, who were full digitalis and diuretics therapy, in order to investigate hemodynamic response, the duration of effects, dose response effects, drug concentration, tachy-phylaxis after continuous use and adverse side effects.

A significant increase was found in cardiac index, stroke index, and left ventriculer stroke work index.

A feature of this drug appears to be reduction of the preload, while slight influencing the heart rate and arterial mean pressure.

Cardiotonic effects of the drug began to appear 30 min after oral administration, as shown by the increase in cardiac index. Such a significant (p<0. 05) increase persisted for 5 h after a single dose of 40 mg, and similar effects were observed with a 20 mg dosage.

There was a similar decrease in pulmonary capillary wedge pressure. More marked effects on hemodynamic parameters were found in 40 mg group compared with the patients receiving 20 mg.

The plasma concentration of TA-064 increased dose dependently and reached a peak value 1.0~1.5 h after oral administration. In the measurement of cases with continuous administration, conspicuous accumulation of the drug was not seen.

In nine patients who were given the drug every day and examined after 1 month of administration, conside-rable improvements was made in body weight cardio-thoracic ratio and clinical symptoms.

These results indicated the beneficial effects of TA-064.