Pharmacodynamics of enoximone during intravenous infusion

Abstract

Twenty-one patients with heart failure (NYHA class II-IV) received a 24-hour infusion of enoximone, followed by a 12-hour washout period. Patients were randomly assigned to one of four treatment groups. Groups I-III received a 0.5 mg/kg bolus, followed by a maintenance infusion of 2.5, 5.0 or 10.0 micrograms/kg/minute. Group IV patients received a maintenance infusion of 5.0 micrograms/kg/minute without the bolus. Serial assessments of haemodynamics, plasma levels of enoximone and enoximone sulphoxide, and ventricular ectopy were performed. Enoximone produced a significant increase in cardiac index (28.1-46.7%) and a decrease in mean pulmonary artery wedge pressure (6.4-35.7%) and systemic vascular resistance (34.7-78.9%). Enoximone had minimal effect on heart rate and blood pressure. In patients who did not receive an initial bolus of 0.5 mg/kg, haemodynamic changes were delayed by approximately 1 hour. Significant haemodynamic improvement was noted at even the lowest infusion rate and did not increase in linear fashion at higher infusion rates. During infusion of enoximone at 10.0 micrograms/kg/minute, both enoximone and its sulphoxide accumulated non-linearly and did not achieve a steady state. No significant adverse effects were noted in these patients. Enoximone infusion at rates greater than 5.0 micrograms/kg/minute may confer minimal additional haemodynamic benefit, while resulting in significant accumulation of enoximone and enoximone sulphoxide. Ventricular ectopy did not increase significantly in most patients.