Reduction of the acute bioavailability of metformin by the alpha-glucosidase inhibitor acarbose in normal man.
In a double-blind cross-over study, we investigated a possible influence of the alpha-glucosidase inhibitor acarbose on the bioavailability of the biguanide compound metformin. Each of the six healthy young male volunteers was randomly allocated during two consecutive 7 day periods to either acarbose (days 1-3: 3 x 50 mg day-1; days 4-7: 3 x 100 mg day-1) or placebo. At day 7 and 14 of the study, the overnight-fasted subjects ingested 1000 mg metformin with the first bite of a standardized breakfast (500 kcal; 60 g carbohydrates) and together with either placebo or 100 mg acarbose. Acarbose significantly (P < 0.05) reduced the meal-induced increase in blood glucose and plasma insulin levels. Acarbose induced a significant (P < 0.05) reduction in early (90, 120, 180 min) serum levels, peak concentrations (Cmax: 1.22 +/- 0.14 vs. 1.87 +/- 0.60 mg l-1) and area under the curve of metformin (AUC 0-540 min: 423 +/- 55 vs. 652 +/- 55 mg min l-1), but did not diminish its 24 h urinary excretion. In conclusion, acarbose significantly reduces the acute bioavailability of metformin in normal subjects.
Scheen
A J
AJ
Department of Medicine, CHU Sart Tilman, Liège, Belgium.
de Magalhaes
A C
AC
Salvatore
T
T
Lefebvre
P J
PJ
D020909:Acarbose; D000328:Adult; D001682:Biological Availability; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D018592:Cross-Over Studies; D004311:Double-Blind Method; D065089:Glycoside Hydrolase Inhibitors; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000097:blood; D008297:Male; D008687:Metformin / Q000097:blood / Q000493:pharmacokinetics*; D012016:Reference Values; D014312:Trisaccharides / Q000494:pharmacology*
D001786:Blood Glucose; D065089:Glycoside Hydrolase Inhibitors; D007004:Hypoglycemic Agents; D007328:Insulin; D014312:Trisaccharides; D008687:Metformin; D020909:Acarbose