Pharmacology and pharmacokinetics of enoximone.

ABSTRACT

Enoximone is an inotropic vasodilating agent. Its principal effects are positive inotropism and vasodilation, which are not accompanied by changes in myocardial oxygen consumption. An inotropic dose of enoximone increases the level of cyclic AMP in the isolated, blood-perfused dog papillary muscle owing to its selective inhibition of the one isoform of cyclic AMP phosphodiesterase from the dog heart that is inhibited by cyclic GMP. Studies on the metabolism and pharmacokinetic profile of enoximone have been carried out in the rat, dog and monkey. Enoximone is metabolized mainly by oxidation to enoximone sulphoxide in all species studied, and this is reversible. In congestive heart failure patients, approximately 74% of a rapidly administered intravenous dose of enoximone is excreted in a 24-hour urine collection as the sulphoxide metabolite; only about 0.49% is recoverable as intact drug. Enoximone sulphoxide has the same inotropic and vasodilator activities as enoximone but is 0.13-0.14 times as potent and has a 13 times longer duration of inotropic action in the dog. It is suggested that the metabolite may contribute to some of the effects that follow enoximone administration.