Absorption of Digoxin from Tablets and Capsules in Subjects with Malabsorption Syndromes

Abstract

The relative steady-state bioavailability of two oral digoxin dosage forms was studied in 17 subjects with malabsorption syndromes. Male subjects received the following treatments in randomized crossover fashion for 14 days: three 0.125-mg digoxin tablets or three 0.1-mg digoxin capsules once daily. Female subjects received digoxin on the same schedule but at two-thirds the dose. Serum and urine samples were collected and analyzed for digoxin by radioimmunoassay, and treatments were compared by evaluating pharmacokinetic parameters. The mean area under the serum concentration versus time curve for tablets (28.1 h.nmol/L [21.9 h.ng/mL]) was smaller (p less than 0.03) than that for capsules (31.1 h.nmol/L [24.3 h.ng/mL]), and the mean maximum serum digoxin concentration for tablets (2.9 nmol/L [2.3 ng/mL]) was lower (p less than 0.02) than that for capsules (4.0 nmol/L [3.1 ng/mL]). There was no difference in cumulative urinary excretion of digoxin between the two treatments. In contrast to previous reports, we observed that digoxin from Lanoxin Tablets appears to be well absorbed in subjects with malabsorption. Nevertheless, these subjects absorbed digoxin from capsules better than from tablets, with the greatest differences occurring in subjects without a colon and in those subjects with the lowest serum carotene concentrations.

The Impact of Intestinal Failure on Oral Drug Absorption: A Review

“…20 Changing formulation to elixir or gel capsules may improve digoxin bioavailability, as demonstrated in patients with small intestine malabsorption. 22 The compensatory ability of the colon to absorb digoxin may enable therapeutic concentrations to be achieved in patients after resection of the small intestine. 23 However, a case report of a patient with an end jejunostomy demonstrated poor absorption, resulting in failure to achieve therapeutic serum concentrations from tablets, gel capsules, and elixir at doses up to 750μg/day.…”

All disease begins in the gut: Influence of gastrointestinal disorders and surgery on oral drug performance

“…Untreated celiac disease can on the other hand increases the absorption of numerous orallydelivered drugs, including antibiotics (Mattila et al, 1973), aspirin (Parsons et al, 1977), methyldopa (Renwick et al, 1983), simvastatin (Moron et al, 2013), β-blockers (Kitis et al, 1982a) and levothyroxine (Collins et al, 2012) but decreases digoxin absorption (Heizer et al, 1989). The specific mechanisms underlying these effects on drug malabsorption in celiac disease are more extensively reviewed by Wang et al (2014), though briefly are thought to include rapid gastric emptying (Moberg and Carlberg.G, 1974), changes to intraluminal pH (Kitis et al, 1982a), abnormal mucosal permeability (Parsons, 1977), and enzyme deficiencies that may be associated with villous atrophy and reduced first-pass metabolic effects (Lang et al, 1996).…”