経口β1-agonist, denopamineの薬剤耐性に関する検討

A study on tolerance to denopamine, oral β1-agonist

　慢性心不全患者23例（NYHAII-III）にデノパミン30mgを約40H間投与し，その前後で10mgの単回投与試験を心エコー法・パルスドプラー法を用いて行った。これらデノパミンの慢性効果，初回単回効果，および慢性投与後の単回効果を評価することにより薬剤耐性の有無を検討した。1）デノパミン慢性投与により血圧，心拍数には有意な変化はなかったが，左室拡張末期径は有意に減少し，短径短縮率（％FS），平均円周線維短縮速度（mVCF），心係数（CI）は有意に増加した。2）初回単回投与では平均血圧心拍数は有意に増加し，％FS，mVCF，CIも有意に増加した。3）慢性期単回投与でも平均血圧，心拍数は有意に増加し，％FS，mVCF，CIも増加した。4）慢性投与前後で単回投与による％FS，mVCF，CIの変化量には有意差はなかった。

　デノパミンの慢性投与によってβ-receptorのdown regulationなどによる薬剤耐性をきたさない可能性が示唆された。

To investigate whether effects of denopamine be-come weaker or not. Initial single dose (10mg) effects, single dose effects after long-term treatment (30 mg per day, about 40 days), and chronic effects were studied by Doppler and echocardiography in 23 patients with heart failure (NYHA II-III). 1) Chronic effects: Blood pressure and heart rates didn't change significantly whether they were measured before or after long-term treatment. But left ven-tricular end-diastolic dimension decreased from 54.6±10.2 to 53.3±10.1mm (p＜0.01). Percent frac-tional shortening (%FS) increased from 22.6±7.8 to 25.3±8.6% (p＜0.05). Mean velocity of circum-ferential fiber shortening (mVCF) tended to in-crease, and cardiac index (CI) increased from 2.71 ±0.47 to 2.98±0.57l/min/m²(p＜0.01). 2) Initial single dose effects: Blood pressure and heart rates increased significantly. %FS increased from 25.0±7.7 to 25.9±7.8% (p＜0.05), mVCF increased from 0.94±0.26 to 1.03±0.28 circ/sec (p＜0.01), and CI increased from 2.81±0.49 to 3.09±0.49l/min/m ²(p＜0.01). 3) Single dose effects after long-term treat-ment: Blood pressure and heart rates increasedsignificantly. %FS tended to increase, mVCF in-creased from 1.02±0.27 to 1.09±0.30 circ/sec (p＜0.05), and CI increased from 3.05±0.62 to 3.37±0.54l/min/m ² (p＜0.01). 4) Comparison of single dose effects before and after long-term treatment: Single dose effects on the hemodynamics (changes in %FS, mVCF, and CI) were not significantly different whether they were administrated over a long-term or not.

These results suggest that denopamine has inotro-pic action even when long-term treatment is carried out.