Pharmacokinetics and pharmacodynamics of muzolimine in chronic heart failure

The aim of the present study was to investigate muzolimine pharmacokinetics and pharmacodynamics in chronic heart failure. We report preliminary results from 6 patients, aged 64.2 years (range 54-73), in chronic heart failure (NYHA class III). All patients had lowered ejection fraction determined by echocardiography, and increased heart volume determined by cardiac X-ray. They were under treatment with long-term digitoxin with serum digitoxin concentrations within or below the therapeutic range. We investigated muzolimine pharmacokinetics on day 1 of treatment and after 28 days. Heart rate and rhythm were monitored with 24 hours ECG recording and analyzed on an Avionics Arrhythmia Analyzer. Heart rate, cardiac volume, ejection fraction and laboratory findings were not significantly changed between day 1 and day 28 of treatment. The time for peak absorption ranged between 1.5 and 6 hours on day 1 and 1.0 and 3 hours on day 28. The peak concentration was significantly higher on day 28. No significant difference was found in the areas under the concentration curves, serum elimination half-lives and renal clearances after acute and chronic administration. In the first 4 patients studied, we found ventricular and supraventricular arrhythmias before treatment and after 28 days on muzolimine. These preliminary data indicate a change in the pharmacokinetics of muzolimine on chronic dosing with more rapid absorption, higher peak concentrations, and increased area under the other plasma concentration curves.