PHARMACOKINETICS OF DIGOXIN ADMINISTERED TO HORSES WITH CONGESTIVE-HEART-FAILURE

Nine horses with (naturally acquired) congestive heart failure were tr eated with 2.2 mug of digoxin/kg of body weight by the IV route, follo wed by 11 mug/kg administered orally every 12 hours thereafter. Furose mide was administered IV concurrently with iv administered digoxin eve ry 12 hours. Serum concentration of digoxin was measured after the fir st (IV) and seventh (orally administered) dose. After IV administratio n, digoxin disposition was described by a 2-compartment model, with a rapid distribution phase (t1/2alpha = 0.17 hour), followed by a slower elimination phase (beta = 0.096 +/- 0.05 5 h-1, t1/2beta = 7.2 hours, where beta is the exponential term from the elimination phase of the concentration vs time curve). Bioavailability after oral administratio n was 21.2 +/- 10.8%. After the seventh orally administered dose, seru m concentration of digoxin peaked 1 to 2 hours later, and was 1.9 +/- 0.7 ng/ml (mean +/- SD). In 4 horses, a second increase in serum digox in concentration was observed 4 to 8 hours after the initial peak, whi ch possibly was evidence of enterohepatic recycling of the drug. Respo nse to treatment included reduction in heart rate, peripheral edema, a nd pulmonary edema, but these could not be attributed to the digoxin a lone because the horses were treated concurrently with furosemide.