Lack of tolerance development during chronic ibopamine administration to patients with congestive heart failure

Abstract

Beta-adrenergic agonists can progressively lose their efficacy during chronic therapy in patients with heart failure. Ibopamine is a new dopamine derivative, active on dopaminergic and beta-adrenergic receptors, whose hemodynamic activity has been acutely demonstrated. To assess whether any attenuation of its efficacy occurs, the variations of the cardiac output induced during chronic therapy were monitored by impedance cardiography in 15 patients with dilated cardiomyopathy who showed a significant increase of the cardiac output (20.7 +/- 10.0%) after acute ibopamine administration. The efficacy of ibopamine was also assessed after 6 and 12 months of therapy by echocardiography, exercise testing, and 24-hour dynamic electrocardiogram (EKG) monitoring. The cardiac output response to ibopamine did not show any significant attenuation (range 15% to 19%) in the evaluations at 1, 2, 3, 4, 8, and 12 months of therapy. No significant change, was noted, after 6 and 12 months, in the exercise capacity (505 vs. 602 and 604 seconds) and the fractional shortening (16.2 vs. 18.3 and 18.5) without any change of the diastolic diameter. Ventricular arrhythmias were significantly reduced after 6, but not 12, months of therapy. No significant change in the New York Association (NYHA) functional class was noted at 6 and 12 months of therapy (2.4 +/- 5 vs. 2.3 +/- 7 and 2.4 +/-0.6, respectively). Our results show that ibopamine can maintain its hemodynamic activity even during chronic therapy.

Other agents

“…Ibopamine is an orally active dopamine agonist which has been shown to activate dopaminergic receptors DA1 and DA2 at daily doses of 100–200 mg, β–adrenergic receptors at 300–400 mg, and α‐adrenergic receptors at greater than 400 mg 6,7 . Its pharmacological effect is maintained over prolonged periods 8,9 . Both in normal subjects and in patients with mild renal impairment, ibopamine administration has produced an increase in renal plasma flow, an increase in 99m Tc–DTPA clearance, a reduction in filtration fraction and an increase in sodium excretion and diuresis 10–12 …”