title: Accumulation of metformin by tissues of the normal and diabetic mouse.
abstract: 1. Tissue accumulation of the antihyperglycaemic agent metformin (dimethylbiguanide) was examined after oral administration to the normal and streptozotocin (STZ) diabetic mouse. 2. Metformin (50 mg/kg body weight containing 14C-metformin 25 microCi/kg body weight), which is stable and not metabolized, resulted in maximum plasma concentrations at 0.5 h which declined to < 5% of maximum by 24 h. Maximum plasma concentrations (mumol/l, mean +/- SE) in the hepatic portal vein (normal 51.7 +/- 5.4, STZ 61.5 +/- 8.0) were higher than in the inferior vena cava (normal 29.0 +/- 2.8, STZ 35.4 +/- 5.9). 3. The greatest accumulation of metformin occurred in tissues of the small intestine, where maximum concentrations were > 1000 mumol/kg wet weight at 0.5-2 h, but declined to < 2% of maximum by 24 h. 4. Stomach, colon, salivary gland, kidney and liver accumulated metformin more than two-fold, and concentrations of the drug in heart and skeletal (gastrocnemius) muscle were greater than plasma concentrations on some occasions up to 8 h. 5. In a separate study, i.v.-administered metformin was selectively accumulated by tissues of the small intestine. Thus, retention of metformin by tissues of the small intestine may represent a deep compartment for the drug.
authors.affiliation: Department of Pharmaceutical and Biological Sciences, Aston University, Birmingham, UK.
authors.forename: C
authors.initials: C
authors.lastname: Wilcock
authors.forename: C J
authors.initials: CJ
authors.lastname: Bailey
mesh_terms: D000284:Administration, Oral; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D004064:Digestive System / Q000378:metabolism; D007275:Injections, Intravenous; D008297:Male; D008687:Metformin / Q000493:pharmacokinetics*; D051379:Mice; D008815:Mice, Inbred Strains; D014018:Tissue Distribution
chemical_list: D008687:Metformin