title: A steady-state evaluation of the effects of propantheline bromide and cholestyramine on the bioavailability of digoxin when administered as tablets or capsules.
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 X 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 less than .0005) and tablets with propantheline (P less than .01). A significant finding was also observed when comparing trough concentrations for tablets alone versus tablets with cholestyramine (P less than .005).(ABSTRACT TRUNCATED AT 250 WORDS)
mesh_terms: D000328:Adult; D001682:Biological Availability; D002214:Capsules; D002792:Cholestyramine Resin / Q000008:administration & dosage*; D004077:Digoxin / Q000008:administration & dosage / Q000097:blood*; D004347:Drug Interactions; D006801:Humans; D008297:Male; D011413:Propantheline / Q000008:administration & dosage*; D011897:Random Allocation; D013607:Tablets
chemical_list: D002214:Capsules; D013607:Tablets; D002792:Cholestyramine Resin; D011413:Propantheline; D004077:Digoxin