Prazosin alters free and total plasma digoxin levels in dogs

Digoxin has been associated with a variety of drug interactions. Studies in our laboratory indicate that single doses of prazosin may alter plasma steady-state digoxin levels. Adult mongrel dogs were given digoxin tablets orally (0.008 mg/kg, twice daily) until steady-state levels of digoxin were reached. Dogs were then tested in a cross-over study with prazosin and saline. Plasma samples were assayed for both free and total plasma digoxin via radioimmunoassay. Free drug was separated from protein bound drug utilizing a micropartition system. Plasma binding of digoxin as well as nonspecific tissue binding was reduced by prazosin and resulted in an increased fraction of free digoxin in plasma. The increase in free digoxin leads to an increase in the pool of digoxin available for pharmacologic activity. Acute experiments demonstrated such an increased pharmacologic effect of digoxin in the presence of prazosin. Prazosin pretreatment prior to a continuous digoxin infusion significantly increased the positive inotropic effect of digoxin compared to dogs receiving only digoxin.