Enoximone is an
imidazole derivative which proved to be a selective inhibitor of the
isoenzymes III/IV of the cAMP-specific
phosphodiesterase. It has been shown in various experimental models that the
drug exerts both positive inotropic and vasodilating properties which can be attributed to the proposed mode of action. A marked dose-dependent improvement in left ventricular pump performance was observed, with only minor changes in heart rate or systemic blood pressure, if
enoximone was administered as i.v. -bolus to patients with moderate to severe
congestive heart failure. These effects coincided with vasodilatory effects as determined by decreases in systemic vascular resistance and pulmonary capillary wedge pressure.
Enoximone is eliminated by intensive metabolism, predominantly in the liver, with
enoximone sulfoxide being the major metabolite in man.
Enoximone exhibits a marked firstpass metabolism following
oral administration. There is evidence in the literature that the metabolism can be saturated either during long-term administration or by increasing the dose of
enoximone. In experimental settings, the metabolite exerts weak positive inotropic effects, too, and reconversion to the parent compound
enoximone has been demonstrated in addition. The half-life of elimination of
enoximone seems to be about 1 h in healthy volunteers and approximately 3 to 7 h in patients with
congestive heart failure, with marked inter-individual differences. In patients with
renal failure mainly
enoximone sulfoxide accumulates in plasma depending on the degree of renal impairment. The elimination of
enoximone seems to be impaired in these patients, too, which might be caused by enhanced reconversion due to the high plasma concentrations of the metabolite.(ABSTRACT TRUNCATED AT 250 WORDS)