Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Traditional IUPAC Name
Độ hòa tan
Freely soluble as HCl salt
pKa (Strongest Basic)
Dược Lực Học :
Metformin is an oral antihyperglycemic agent that improves glucose tolerance in patients with NIDDM, lowering both basal and postprandial plasma glucose. Metformin is not chemically or pharmacologically related to any other class of oral antihyperglycemic agents. Unlike sulfonylureas, metformin does not produce hypoglycemia in either patients with NIDDM or healthy subjects and does not cause hyperinsulinemia. Metformin does not affect insulin secretion.
Cơ Chế Tác Dụng :
Metformin is a biguanide antihyperglycemic agent used for treating non-insulin-dependent diabetes mellitus (NIDDM). It improves glycemic control by decreasing hepatic glucose production, decreasing glucose absorption and increasing insulin-mediated glucose uptake. Metformin is the only oral antihyperglycemic agent that is not associated with weight gain. Metformin may induce weight loss and is the drug of choice for obese NIDDM patients. When used alone, metformin does not cause hypoglycemia; however, it may potentiate the hypoglycemic effects of sulfonylureas and insulin. Its main side effects are dyspepsia, nausea and diarrhea. Dose titration and/or use of smaller divided doses may decrease side effects. Metformin should be avoided in those with severely compromised renal function (creatinine clearance < 30 ml/min), acute/decompensated heart failure, severe liver disease and for 48 hours after the use of iodinated contrast dyes due to the risk of lactic acidosis. Lower doses should be used in the elderly and those with decreased renal function. Metformin decreases fasting plasma glucose, postprandial blood glucose and glycosolated hemoglobin (HbA1c) levels, which are reflective of the last 8-10 weeks of glucose control. Metformin may also have a positive effect on lipid levels. In 2012, a combination tablet of linagliptin plus metformin hydrochloride was marketed under the name Jentadueto for use in patients when treatment with both linagliptin and metformin is appropriate.
Metformin's mechanisms of action differ from other classes of oral antihyperglycemic agents. Metformin decreases blood glucose levels by decreasing hepatic glucose production, decreasing intestinal absorption of glucose, and improving insulin sensitivity by increasing peripheral glucose uptake and utilization. These effects are mediated by the initial activation by metformin of AMP-activated protein kinase (AMPK), a liver enzyme that plays an important role in insulin signaling, whole body energy balance, and the metabolism of glucose and fats. Activation of AMPK is required for metformin's inhibitory effect on the production of glucose by liver cells. Increased peripheral utilization of glucose may be due to improved insulin binding to insulin receptors. Metformin administration also increases AMPK activity in skeletal muscle. AMPK is known to cause GLUT4 deployment to the plasma membrane, resulting in insulin-independent glucose uptake. The rare side effect, lactic acidosis, is thought to be caused by decreased liver uptake of serum lactate, one of the substrates of gluconeogenesis. In those with healthy renal function, the slight excess is simply cleared. However, those with severe renal impairment may accumulate clinically significant serum lactic acid levels. Other conditions that may precipitate lactic acidosis include severe hepatic disease and acute/decompensated heart failure.
Dược Động Học :
▧ Absorption :
Absorbed over 6 hours, bioavailability is 50 to 60% under fasting conditions. Administration with food decreases and delays absorption. Some evidence indicates that the level of absorption is not dose-related, suggesting that absorption occurs through a saturable process. Limited data from animal and human cell cultures indicate that absorption occurs through a passive, non-saturable process, possibly involving a paracellular route. Peak action occurs 3 hours after oral administration.
▧ Volume of Distribution :
654 L for metformin 850 mg administered as a single dose. The volume of distribution following IV administration is 63-276 L, likely due to less binding in the GI tract and/or different methods used to determine volume of distribution.
▧ Protein binding :
Metformin is negligibly bound to plasma proteins.
▧ Metabolism :
Metformin is not metabolized.
▧ Route of Elimination :
Intravenous single-dose studies in normal subjects demonstrate that metformin is excreted unchanged in the urine and does not undergo hepatic metabolism (no metabolites have been identified in humans) nor biliary excretion. Approximately 90% of the drug is eliminated in 24 hours in those with healthy renal function. Renal clearance of metformin is approximately 3.5 times that of creatinine clearance, indicating the tubular secretion is the primary mode of metformin elimination.
▧ Half Life :
6.2 hours. Duration of action is 8-12 hours.
▧ Clearance :
718-1552 mL/minute following single oral dose of 0.5-1.5 g. Metformin is removed by hemodialysis at a rate of approximately 170 ml/min under good hemodynamic conditions.
Độc Tính :
Acute oral toxicity (LD50): 350 mg/kg [Rabbit]. It would be expected that adverse reactions of a more intense character including epigastric discomfort, nausea, and vomiting followed by diarrhea, drowsiness, weakness, dizziness, malaise and headache might be seen.
Chỉ Định :
For use as an adjunct to diet and exercise in adult patients (18 years and older) with NIDDM. May also be used for the management of metabolic and reproductive abnormalities associated with polycystic ovary syndrome (PCOS). Jentadueto is for the treatment of patients when both linagliptin and metformin is appropriate.
Tương Tác Thuốc :
Cimetidine may increase the therapeutic and adverse effects of metformin by increasing its serum concentration. Consider alternate therapy.
Somatropin may antagonize the hypoglycemic effect of metformin. Monitor for changes in fasting and postprandial blood sugars.
Liều Lượng & Cách Dùng :
Tablet - Oral - 2.5MG; 1GM (LINAGLIPTIN; METFORMIN HYDROCHLORIDE)
Tablet - Oral - 2.5MG; 500MG (LINAGLIPTIN; METFORMIN HYDROCHLORIDE)
Tablet - Oral - 2.5MG; 850MG (LINAGLIPTIN; METFORMIN HYDROCHLORIDE)
Tablet - Oral - 500 mg
Tablet - Oral - 850 mg
Tablet, extended release - Oral
Dữ Kiện Thương Mại
Nhà Sản Xuất
Sản phẩm biệt dược : Apo-Metformin
Sản phẩm biệt dược : Fortamet
Sản phẩm biệt dược : Gen-Metformin
Sản phẩm biệt dược : Glucophage
Sản phẩm biệt dược : Glucophage XR
Sản phẩm biệt dược : Glumetza
Sản phẩm biệt dược : Mylan-Metformin
Sản phẩm biệt dược : Novo-Metformin
Sản phẩm biệt dược : Nu-Metformin
Sản phẩm biệt dược : PMS-Metformin
Sản phẩm biệt dược : Ran-Metformin
Sản phẩm biệt dược : Ratio-Metformin
Sản phẩm biệt dược : Riomet
Sản phẩm biệt dược : Sandoz Metformin
Sản phẩm biệt dược : Teva-Metformin
Tài Liệu Tham Khảo Thêm
National Drug Code Directory