[Treatment of chronic cardiac insufficiency with intravenous bolus enoximone. Study of a pharmacokinetic-hemodynamic relation]

Abstract

The aim of this study was to evaluate the efficacy and pharmacokinetics of enoximone administered as an intravenous bolus in 12 patients (mean age 62 years) with severe chronic congestive cardiac failure (Stage IV of the NYHA) due to ischemic (N = 6) or idiopathic (N = 6) cardiomyopathy. The haemodynamic parameters and plasma concentrations of enoximone and its metabolite were measured 15, 30, 60, 90, 120 minutes, 4 and 6 hours, after IV bolus of enoximone 1 mg/kg in 10 minutes. Enoximone increased the cardiac index by an average of 37 p. 100 (1.92 +/- 0.3 to 2.63 +/- 0.35 l/mn/m2; p less than 0.001); pulmonary artery diastolic pressures fell by 33 p. 100 (p less than 0.01). Systemic arterial resistances decreased by 23 p. 100 (p less than 0.05). No significant changes in heart rate or blood pressure were observed. The peak effect was recorded between the 15th and 30th minute. The pharmacokinetic study showed the half life of enoximone to be 2.2 +/- 0.78 hours, the area under the curve to be 2,818 +/- 953, the volume of distribution to be 69.6 +/- 24 l and the total clearance to be 22.8 +/- 8.5 l/hour. The half life of the metabolite was 4.45 +/- 1.05 hours. There was a significant correlation between the percentage increase in cardiac index and peak enoximone concentration (r = 0.91; p less than 0.001). In conclusion, an IV bolus of enoximone is an effective treatment for chronic cardiac failure. The haemodynamic response was related to the peak enoximone plasma concentration.