Digoxin Tablet Bioavailability: Single-Dose and Steady-State Assessment

Variation in the biological availability of digoxin tablets is a significant problem, and the relative accuracy and reliability of various methods of assessing absorption of the glycoside have not been established. In a crossover study, the bioavailability of four lots of digoxin tablets with different dissolution rates was tested in seven normal volunteers after single 0.5-mg doses and 0.5-mg doses were given daily for 9 days. Digoxin preparations that showed marked differences after single doses also showed significant differences by the "steady-state" measurements. Two lots of digoxin from the same manufacturer showed major discrepancies. The single-dose measurements used (peak serum levels, areas under the concentration-time curves, and 24-hour urinary digoxin excretion) did not reliably predict the magnitude of differences found in the steady state when drug products with different rates of absorption were compared. Of the three single-dose measurements, the 24-hour urinary excretion level seemed to be the most reliable screening test.