治療抵抗性慢性うっ血性心不全患者に対する新α1-receptor blocker E-643の急性効果—薬物動態と血行動態による検討

Acute effect of new α1-receptor blocking drug, E-643 in severe congestive heart failure: pharmachokinetic and hemodynamics

　うっ血性心不全とくにいわゆる治療抵抗性心不全に対して，利尿剤やジギタリス薬に加えて血管拡張薬が臨床的に応用されて有効性が認められてきた^1,2）。E-643は新しく開発されたpostsynaptic α-receptor（α₁-receptor）を選択的に阻害すると考えられるα-blockerである^3,16,17）。

　今回，我々は治療抵抗性慢性うっ血性心不全に対するE-643の急性効果を，薬物動態と血行動態より検討したので報告する。

　Estimation of pharmachokinetics and hemodynamics were performed in 6 patients with severe congestive heart failure before and after administration of oral E-643 (2mg), which is a longacting, new α-receptor blocking drug.

　The pharmachokinetic parameters were as follows: Plasma peak concentration level (computer-calculated valves) was 36.2+22.9 (mean 4±SD) ng/ml, time of the peak level was 2.33±0.82 hours and elemination half life of beta phase (TI/2) was 2.31±1.60 hours.

　The hemodynamic parameters were as follows: After administration of E-643, the effects occurred within 1 hours, reached to the maximum at 3 hours and persisted for 5 or 6 hours. At peak effect, cardiac index increased from 1.84±0.30 L/min/m₂ to 2.52±0.47 L/min/m₂, mean right atrial pressure decreased from 9±5 mmHg to 4±2 mmHg, mean pulmonary capillary wedge pressure decreased from 30±10 mmHg to 19±9 mmHg, systemic vascular resistance decreased from 2189±693 dynes･sec･cm_-5 to 1857±256 dynes･sec･cm_-5, and pulmonary vascular resistance decreased from 316±103 dynes･sec･cm_-5 to 236±105 dyne･sec･cm_-5, however heart rate and mean blood pressure remained unchanged.

　Therefore, E-643 seemed to be a longacting vasodialator with both acting preload and after-load reduction and so to be useful for the treatment of severe congestive heart failure as a deloading agent.