The oral absorption of digoxin in tablet form has been reported to be reduced after cancer chemotherapy and radiation therapy because of cancer treatment-induced damage to the intestinal epithelium. We investigated possible differences in the effects of high-dose cancer chemotherapy on the relative bioavailability of digoxin administered in tablet form (Lanoxin; Burroughs Wellcome Co.) and in solution-in-capsule form (Lanoxicaps; Burroughs Wellcome Co.). Each subject received a single oral dose of either 0.5 mg Lanoxin (six subjects) or 0.4 mg Lanoxicaps (seven subjects) both before and after chemotherapy. For Lanoxin, there was a significant reduction in the AUC after chemotherapy to 54.4% +/- 35.5% (mean +/- SD) of the value before chemotherapy (P = 0.02), whereas for Lanoxicaps there was an insignificant reduction in AUC to 85.1% +/- 42.7% of the value before chemotherapy. These findings show that changes in the oral dosage formulation of digoxin from a tablet to a solution-in-capsule form can overcome the adverse effects of high-dose cancer chemotherapy on drug absorption, and suggest a similar approach may be successful for other drugs.