Pharmacokinetics and bioavailability of digoxin capsules, solution and tablets after single and multiple doses

Abstract

The bioavailability of single doses of digoxin capsules (0.4 mg), digoxin solution (0.4 mg) and reference tablets (0.5 mg) was compared with that of single intravenous doses (0.4 mg) of digoxin using measurement of 24 hour urinary excretion and area under the plasma concentration curve. The absolute systemic availability of all three oral preparations was significantly less than 100 percent. The bioavailability of capsules and solution was nearly identical (79 percent and 76 percent, respectively, as assessed with values for area under the concentration curve and 65 percent and 62 percent as assessed with urinary excretion values); both forms had greater systemic availability than the tablet, which had bioavailability values of 50 percent using area under the curve and 41 percent using urinary excretion. Capsules and solution also were similar in peak plasma digoxin levels achieved (3.7 and 3.1 ng/ml), time of peak concentration (0.8 and 0.6 hour after dosage) and apparent first order absorption half-life (11.3 and 10.2 minutes); both capsules and solution differed significantly from tablets (peak level 1.6 ng/ml, time of peak concentration 1.2 hours and absorption half-life 27.1 minutes). Single dose findings were substantiated when steady state plasma levels and 24 hour urinary excretion values were measured from days 11 through 16 of the period of once daily ingestion. Mean plasma levels (0.70 ng/ml) and urinary excretion values (45.1 percent of dose) for capsules were nearly identical to those for solution (0.69 ng/ml and 42.5 percent of the dose), and values for both capsules and solution were significantly greater than those for tablets. Within- and between-subject variation in bioavailability was similar for the three oral preparations. Thus the single dose bioavailability study was predictive of the steady state findings. The bioavailability of digoxin capsules is equivalent to that of a solution and significantly greater than that of a reference tablet formulation.