Metformin absorption

Marathe PH, Wen YD, Norton J, Greene DS, Barbhaiya RH, Wilding IR. Effect of altered gastric emptying and gastrointestinal motility on metformin absorption. Br J Clin Pharmacol 2000 50 325-332. 

The extent of metformin absorption from metformin ER at 2,000 mg once-daily dose is similar to the same total daily dose administered as metformin IR 1,000 mg twice daily. 

Another drawback is the lack of correlation for paracellularly transported compounds. For example, some low molecular weight hydrophilic compounds (e.g., ranitidine, atenolol, furosemide, and metformin) showed poor permeability in the Caco-2 model despite an absorption larger than 50% in humans [168], This is due to the smaller size of the paracellular channels (controlled by tight junctions) in the Caco-2 model compared to human small intestine [146],... 

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. 

T Pancreatic insulin release Metformin Peripheral insulin sensitivity hepatic glucose output/production i intestinal glucose absorption Dose Ist-line (naive pts), 1.25/250 mg PO daily-bid 2nd-line, 2.5/500 mg or 5/500 mg bid (max 20/2000 mg) take w/ meals, slowly T dose hold before 48 h after ionic contrast media Caution [C, -] Contra SCr >1.4 mg/dL in females or >1.5 mg/dL in males hypoxemic conditions (sepsis, recent MI) alcoholism metabolic acidosis liver Dz Disp Tabs SE HA, hypoglycemia, lactic acidosis, anorexia, N/V, rash Additional Interactions T Effects W/ amiloride, ciprofloxacin cimetidine, digoxin, miconazole, morphine, nifedipine, procainamide, quinidine, quinine, ranitidine, triamterene,... 

Metformin improves glucose tolerance in NIDDM subjects by lowering both basal and postprandial plasma glucose. Metformin decreases hepatic glucose production, decreases intestinal absorption of glucose and improves insulin sensitivity (increases peripheral glucose uptake and utilization). 

The most common toxic effects of metformin are gastrointestinal (anorexia, nausea, vomiting, abdominal discomfort, and diarrhea), which occur in up to 20% of patients. They are dose-related, tend to occur at the onset of therapy, and are often transient. However, metformin may have to be discontinued in 3-5% of patients because of persistent diarrhea. Absorption of vitamin B12 appears to be reduced during long-term metformin therapy, and annual screening of serum vitamin B12 levels and red blood cell parameters has been encouraged by the manufacturer to determine the need for vitamin B12 injections. In the absence of hypoxia or renal or hepatic insufficiency, lactic acidosis is less common with metformin therapy than with phenformin therapy. 

Acarbose reduces the absorption of metformin (79), as does miglitol (77). 

Metformin can cause reduced vitamin Bi2 absorption, reducing serum Bi2 concentrations and causing megaloblastic anemia (87), the prevalence of which was 9% in 600 patients with type 2 diabetes taking biguanides (phen-formin or metformin) for a mean of 12 years (88). In 353 patients with type 2 diabetes, treated with insulin, who took metformin for 16 weeks in a placebo-controlled study, metformin increased serum homocysteine concentrations by 4% and reduced serum folate by 7% and vitamin Bi2 by 14% (89). 

Megaloblastic anemia is rare with metformin, but vitamin Bi2 concentrations can be reduced by metformin and phenformin (92) because of reduced absorption, and pre-existing deficiency can be exacerbated (64). 

Metformin can be effectively combined with miglitol (SEDA-25, 514) but metformin may accumulate in the gastrointestinal wall, and the combination of metformin with acarbose or miglitol may reduce the absorption of metformin (136,137). 

The authors suggested that chronic diarrhea induced by orlistat could have led to impaired renal function or that orlistat could have increased the absorption of metformin by reducing fat absorption. 

Guar gum 1. Metformin 2. Glibendamide May lead to t blood sugar levels 1 absorption of metformin and glibendamide Avoid concomitant use. Monitor blood sugar closely if either drug is introduced... 

Metformin is mainly absorbed in the upper part of the GI tract with high tendency to adsorb to the intestinal epithelium owing to its ionized nature at physiological pH, and thus its absorption patterns are affected (mainly paracellular), and it causes remarkable GI side effect. This fact, together with the finding that metformin active sites are mainly found in the GI tract and the liver, makes metformin a good candidate for GRDF.f" The blood concentrations of metformin... 

Metformin (Glucophage) Decreases the absorption of glucose from the small intestine and may increase insulin receptor sensitivity as well as peripheral glucose uptake at the cellular level. Does not produce hypoglycemia or hyperglycemia. Can cause GI disturbances. 

Metformin has an absolute oral bioavailability of about 50-60% of the dose after oral application of a single dose. Deconvolution analysis showed that after a short lag-time, the available remainder of the oral dose was absorbed at an exponential rate over about 6 h (Tucker et al., 1981). The bioavailability of phenformin seems to be more variable but also in the range of about 50% (Beckmann, 1968 Travis and Sayers, 1970). In general, absorption of biguanides is slower than their elimination, hence the plasma levels follow flip-flop kinetics (Pentikainen et al., 1979). 

Malabsorption of vitamin B12 was observed in 14 of 46 diabetics taking metformin or phenformin (Callaghan et al., 1980 Adams et al., 1983) metformin was more often to blame. Withdrawal of the drug resulted in normal absorption in only 7 of the 14 (Adams et al., 1983). 

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