A Steady‐State Evaluation of the Effects of Propantheline Bromide and Cholestyramine on the Bioavailability of Digoxin When Administered as Tablets or Capsules

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Abstract
Drug interactions can profoundly alter the absorption of digoxin in tablet form. This study evaluated whether digoxin solution in capsules, a new dosage form with 90% to 100% bioavailability, would reduce such alterations, specifically those caused by cholestyramine and propantheline bromide. The investigation used a six‐treatment, steady‐state, balanced, incomplete block design with 18 healthy adults studied for four continuous two‐week treatment periods. Treatments were either two 0.25 mg digoxin tablets or two 0.20 mg digoxin capsules administered alone, with propantheline, 15 mg qid, or with cholestyramine, 8 g qd. Bioavailability was determined from steady‐state, 24‐hour area under the serum concentration‐time curve (AUC, ng × h/mL) and from 0‐ and 24‐hour trough serum digoxin concentrations (ng/mL). The AUCs for tablets alone, with cholestyramine, and with propantheline were 32.8 ± 13.3 (± SD), 22.4 ± 12.1, and 40.6 ± 13.9, respectively, while corresponding values for capsules were 31.7 ± 9.3, 24.7 ± 7.9, and 35.9 ± 12.8. The trough concentrations for tablets alone, with cholestyramine, and with propantheline were 0.88 ± 0.47, 0.61 ± 0.38, and 1.09 ± 0.35, respectively; trough concentrations for capsules were 0.77 ± 0.28, 0.74 ± 0.28, and 0.96 ± 0.48, respectively. The only significant differences in AUC were seen when comparing tablets alone versus tablets with cholestyramine (P < .0005) and tablets with propantheline (P < .01). A significant finding was also observed when comparing trough concentrations for tablets alone versus tablets with cholestyramine (P < .005). The results confirm (1) bioequivalence of 0.20 mg capsules versus 0.25 mg tablets, (2) significant alterations in tablet bioavailability due to cholestyramine and propantheline, and (3) reduction of these alterations by the capsule dosage form. These findings suggest that digoxin capsules may offer clinical advantages over digoxin tablets in achieving predictable, consistent serum digoxin concentrations in patients receiving cholestyramine, propantheline, and similar drugs.