Pharmacokinetic interactions with digoxin.

Numerous pharmacological agents have been shown to produce clinically significant pharmacokinetic interactions with digoxin. Drugs which reduce digoxin absorption include the antacids aluminium hydroxide, magnesium hydroxide and magnesium trisilicate, the antidiarrhoeals kaolin and pectin, the hypocholesterolaemic agent cholestyramine and the chemotoxins cyclophosphamide, vincristine and bleomycin. Certain antibiotics including sulphasalazine, neomycin and aminosalicylic acid reduce digoxin absorption while others, including erythromycin and tetracycline, increase the bioavailability of digoxin in some patients. Capsule preparations of digoxin in solution are less subject to several of the interactions which affect the absorption and bioavailability of digoxin tablets. Various drugs induce alterations in the volume of distribution and clearance of digoxin. Cardiac patients receiving digoxin therapy are particularly prone to interactions with commonly co-administered medications such as the antiarrhythmics quinidine and amiodarone, the calcium channel blockers verapamil and nifedipine, and possibly some vasodilating agents. Studies of digoxin interactions have yielded discrepant results, indicating the need for careful analysis of investigational design before arriving at clinical conclusions.

Comparative effects of verapamil and isradipine on steady-state digoxin kinetics.

The effects on the steady-state digoxin pharmacokinetics of verapamil (240 mg/day) and a new dihydropyridine calcium channel blocker, isradipine (15 mg/day), were compared. Nineteen healthy white men, aged 23 to 40 years, ingested 0.25 mg digoxin tablets every 12 hours for two consecutive periods of 2 weeks. Each subject also received one of the calcium channel blockers during one of these periods, with agent and sequence randomized. Analyst-blind RIA serum digoxin determinations demonstrated that the nine subjects who received isradipine, 5 mg t.i.d., had a small increment in peak digoxin level from 2.3 +/- 0.6 to 2.9 +/- 0.7 ng/ml (p less than 0.05) but no significant change in steady-state level or AUC over 12 hours. By contrast, the 10 subjects who received verapamil, 80 mg t.i.d., showed significant increases in steady-state (0.9 +/- 0.1 to 1.3 +/- 0.2 ng/ml; p less than 0.001) and peak serum digoxin concentrations (2.5 +/- 0.7 to 3.6 +/- 0.8 ng/ml; p less than 0.001) and in AUC (15.7 +/- 1.7 to 23.6 +/- 2.9 ng . hr/ml; p less than 0.001). Neither calcium channel blocker reduced renal digoxin clearance. Verapamil increases digoxin levels without affecting renal clearance. Isradipine has no clinically important interaction with digoxin.

The effect of dietary fiber on the bioavailability of digoxin in capsules.

Sixteen healthy volunteers were regularly given 0.4 mg of digoxin daily as two capsules with breakfast. After ten days during which breakfast was supplemented with 11 g of bran fiber, steady-state predose mean serum digoxin was lower (0.89 +/- 0.19 versus 0.84 +/- 0.18 ng/mL, P less than .05) and mean 24-hour area under curve determination was lower (30.5 +/- 6.1 versus 28.4 +/- 6.0 ng X hr/mL, P less than .05) than during the control period without bran. Height and time of peak serum digoxin, and 24-hour urinary digoxin were not significantly different. The 6 to 7% reduction in digoxin absorption from capsules is less than that reported from tablets and is probably clinically unimportant.