Metformin distribution

Wang, D. S., Jonker, J. W., Kato, Y., Kusuhara, H., Schinkel, A. H., Sugiyama, Y., Involvement of organic cation transporter 1 in hepatic and intestinal distribution of metformin,... 

Absorption/Distribution - The absolute bioavailability of metformin IR 500 mg given under fasting conditions is approximately 50% to 60%. Food decreases the extent and slightly delays the absorption of metformin. 

Octl (Slc22al) is expressed in the liver and kidney (112,113), while OCT1 is expressed predominately in the kidney (114). Octl is localized to the sinusoidal membrane of the hepatocytes surrounding the central vein and basolateral membrane in the kidney (115,116). Although the membrane localization has not been determined, Octl is likely expressed in the basolateral membrane of the small intestine since the distribution of metformin and intestinal excretion of tetrae-thylammonium (TEA) following intravenous injection was decreased in Octl(-/-) mice (117,118). The reduction in the distribution of metformin in Octl(-/-) was the most prominent in the duodenum followed by jejunum and ileum, but unchanged in the colon, which was consistent with the mRNA of Octl distribution from... 

Metformin is rapidly distributed, and accumulates in these tissues in which the drug possesses most of its activity (muscles, intestine, liver). For buformin, diffusion in the peripheral compartment is reported to be faster than the rediffusion, leading to an accumulation in the respective tissues (Lintz et al., 1974). Plasma protein binding of the biguanides is only about 20% (Garret et al., 1972) or even undetectable (Rang and Dale, 1991). 

Pharmacokinetics. Metformin has approximately 50% to 60% oral bioavailability, low lipid solubility, and a volume of distribution that approximates body water. Metformin is not metabolized and does not bind to plasma proteins. Metformin is eliminated by renal tubular secretion and glomerular filtration. The average half-life of metformin is 6 hours, though pharmacodynamically, metformin s an-tihyperglycemic effects last >24 hours. 

Metformin is quickly absorbed from the small intestine. Bioavailability is from 50 to 60%, and the drug is not protein bound. Peak plasma concentrations occur at approximately 2 hours. The drug is widely distributed in the body and accumulates in... 

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