Pharmacokinetics of a single oral dose of muzolimine in cardiac failure.

The pharmacokinetics of a new "high ceiling" diuretic, muzolimine (Bay g 2821), were investigated after a single oral dose of 40 mg in 7 patients with cardiac failure (Stages I-IV, New York Heart Association classification), and in 2 healthy subjects. Plasma concentrations peaked 1-3 h after administration and declined according to a two-compartment model. The alpha-phase (distribution phase) lasted until 12-16 h after administration and the mean t 1/2 a was 3.6 h (range 2.3-4.7) in patients, and 2.6 h (range 2.3-2.9) in healthy subjects. The mean t 1/2 beta was 13.5 h (range 7.4-22.4) in the patients and 14.0 h (range 12.4-14.6) in healthy subjects. T 1/2 beta was not correlated with the degree of heart failure or with the area beneath the plasma concentration curve, which varied three-fold. The renal clearance of muzolimine was in the range 2.7-15.3 ml . min-1 in 5 subjects in whom it was investigated. The pharmacokinetics of muzolimine appear not to be significantly altered by cardiac failure. The prolonged half-lives of the drug are probably responsible for the longer duration of diuretic action reported for muzolimine than for furosemide and bumetamide.