Do therapeutic doses of acarbose alter the pharmacokinetics of digoxin?
BACKGROUND
Acarbose has become an important adjuvant therapy for diabetic patients. Many of these patients are also treated with digoxin for congestive heart failure or chronic atrial fibrillation.


OBJECTIVE
To evaluate a possible drug interaction between acarbose and digoxin.


METHODS
An open-label, analyst-blind, randomized, crossover, two-period study was conducted in 11 healthy subjects. In period I, each subject received one single oral dose of 0.75 mg digoxin. In period II, they were given acarbose tablets, 50 mg 3 times a day for 12 days. On day 8, one hour after acarbose administration, a single oral dose of 0.75 mg digoxin was administered. The study periods were separated by a 3 week washout interval. Serum digoxin levels, over time, in the two periods were compared by standard techniques.


RESULTS
There were no differences in the pharmacokinetic parameters of digoxin in the two periods, apart from a significant increase in the mean maximum serum concentration (Cmax) when digoxin was given with acarbose (5.97 compared to 4.67 g/L, P = 0.02). Simulated steady-state peak levels of digoxin (Cmax,ss) achieved with a daily dose of 0.25 mg digoxin, in the presence and absence of acarbose, were 2.89 and 2.40 g/L respectively (P = 0.05). Simulated steady-state trough (Cmin,ss) and average (Cave,ss) concentrations were similar and within the therapeutic window.


CONCLUSIONS
There was no significant pharmacokinetic interaction between digoxin and acarbose at current therapeutic doses in the healthy volunteers. This interaction should be further studied with higher doses of acarbose and at steady-state conditions.
Cohen
Eytan
E
Recanati Center for Medicine and Research, Clinical Pharmacology Unit, Rabin Medical Center, Beilinson Campus, Petah Tiqva, Israel.
Almog
Shlomo
S
Staruvin
Daniel
D
Garty
Moshe
M
D020909:Acarbose / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D000284:Administration, Oral; D000328:Adult; D000889:Anti-Arrhythmia Agents / Q000097:blood / Q000493:pharmacokinetics*; D002316:Cardiotonic Agents / Q000097:blood / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D003627:Data Interpretation, Statistical; D004077:Digoxin / Q000097:blood / Q000493:pharmacokinetics*; D004347:Drug Interactions; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D008962:Models, Theoretical; D012044:Regression Analysis; D013607:Tablets; D013997:Time Factors
D000889:Anti-Arrhythmia Agents; D002316:Cardiotonic Agents; D007004:Hypoglycemic Agents; D013607:Tablets; D004077:Digoxin; D020909:Acarbose