Details
Stereochemistry | ABSOLUTE |
Molecular Formula | C25H43NO18 |
Molecular Weight | 645.6048 |
Optical Activity | UNSPECIFIED |
Defined Stereocenters | 18 / 18 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
[H][C@]1(O[C@H]([C@H](O)CO)[C@H](O)[C@@H](O)C=O)O[C@H](CO)[C@@H](O[C@@]2([H])O[C@H](C)[C@@H](N[C@@]3([H])C=C(CO)[C@@H](O)[C@H](O)[C@H]3O)[C@H](O)[C@H]2O)[C@H](O)[C@H]1O
InChI
InChIKey=CEMXHAPUFJOOSV-XGWNLRGSSA-N
InChI=1S/C25H43NO18/c1-7-13(26-9-2-8(3-27)14(33)18(37)15(9)34)17(36)20(39)24(41-7)44-23-12(6-30)42-25(21(40)19(23)38)43-22(11(32)5-29)16(35)10(31)4-28/h2,4,7,9-27,29-40H,3,5-6H2,1H3/t7-,9+,10+,11-,12-,13-,14-,15+,16-,17+,18+,19-,20-,21-,22-,23-,24-,25-/m1/s1
Acarbose is an anti-diabetic drug used to treat type 2 diabetes mellitus and, in some countries, prediabetes. Acarbose is an oligosaccharide which is obtained from fermentation processes of a microorganism, Actinoplanes utahensis, and is chemically known as O-4,6-dideoxy¬ 4-[[(1S,4R,5S,6S)-4,5,6-trihydroxy-3-(hydroxymethyl)-2-cyclohexen-1-yl]amino]¬ α-D-glucopyranosyl-(1 → 4)-O-α-D-glucopyranosyl-(1 → 4)-D-glucose. Acarbose is a complex oligosaccharide that delays the digestion of ingested carbohydrates, thereby resulting in a smaller rise in blood glucose concentration following meals. As a consequence of plasma glucose reduction, PRECOSE (acarbose tablets) reduces levels of glycosylated hemoglobin in patients with type 2 diabetes mellitus. Systemic non-enzymatic protein glycosylation, as reflected by levels of glycosylated hemoglobin, is a function of average blood glucose concentration over time. In contrast to sulfonylureas, PRECOSE does not enhance insulin secretion. The antihyperglycemic action of acarbose results from a competitive, reversible inhibition of pancreatic alpha-amylase and membrane-bound intestinal alpha-glucoside hydrolase enzymes. Pancreatic alpha-amylase hydrolyzes complex starches to oligosaccharides in the lumen of the small intestine, while the membrane-bound intestinal alpha-glucosidases hydrolyze oligosaccharides, trisaccharides, and disaccharides to glucose and other monosaccharides in the brush border of the small intestine. In diabetic patients, this enzyme inhibition results in a delayed glucose absorption and a lowering of postprandial hyperglycemia. Because its mechanism of action is different, the effect of PRECOSE to enhance glycemic control is additive to that of sulfonylureas, insulin or metformin when used in combination. In addition, PRECOSE diminishes the insulinotropic and weight-increasing effects of sulfonylureas. Acarbose has no inhibitory activity against lactase and consequently would not be expected to induce lactose intolerance.
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
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Target ID: CHEMBL2045 |
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Target ID: CHEMBL2608 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16702880 |
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Target ID: CHEMBL2074 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16702880 |
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Target ID: CHEMBL2748 Sources: https://www.ncbi.nlm.nih.gov/pubmed/2962844 |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
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Palliative | PRECOSE Approved UseAcarbose Tablets are indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. Launch Date1995 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
49 ng/mL |
200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered: |
ACARBOSE unknown | Homo sapiens population: HEALTHY age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
0.51 μg × h/mL |
300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered: |
ACARBOSE unknown | Homo sapiens population: HEALTHY age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
|
3.13 μg × h/mL |
0.4 mg/kg single, intravenous dose: 0.4 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered: |
ACARBOSE unknown | Homo sapiens population: HEALTHY age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
0.55 h |
0.4 mg/kg single, intravenous dose: 0.4 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered: |
ACARBOSE unknown | Homo sapiens population: HEALTHY age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
Doses
Dose | Population | Adverse events |
---|---|---|
100 mg 3 times / day multiple, oral (max) Recommended Dose: 100 mg, 3 times / day Route: oral Route: multiple Dose: 100 mg, 3 times / day Sources: |
unhealthy, 57.2 n = 84 Health Status: unhealthy Condition: diabetes mellitus Age Group: 57.2 Sex: M+F Population Size: 84 Sources: |
Disc. AE: Flatulence, Diarrhea... AEs leading to discontinuation/dose reduction: Flatulence (26%) Sources: Diarrhea (17%) Abdominal pain (7%) |
300 mg 1 times / day multiple, oral (max) Recommended Dose: 300 mg, 1 times / day Route: oral Route: multiple Dose: 300 mg, 1 times / day Sources: |
unhealthy, 63 n = 1954 Health Status: unhealthy Condition: diabetes mellitus, type 2 Age Group: 63 Sex: M+F Population Size: 1954 Sources: |
Other AEs: Flatulence, Diarrhea... Other AEs: Flatulence (68 patients) Sources: Diarrhea (13 patients) Loose stools (1 patient) Abdominal pain (4 patients) Nausea (3 patients) Constipation (1 patient) Hypoglycaemic episode (10 patients) Appetite lost (2 patients) Weight loss (1 patient) Burning anal (1 patient) Heartburn (1 patient) |
300 mg 1 times / day multiple, oral (max) Recommended Dose: 300 mg, 1 times / day Route: oral Route: multiple Dose: 300 mg, 1 times / day Sources: |
unhealthy, 63 n = 27803 Health Status: unhealthy Condition: diabetes mellitus Age Group: 63 Sex: M+F Population Size: 27803 Sources: |
Other AEs: Flatulence, Diarrhoea... Other AEs: Flatulence (13.7%) Sources: Diarrhoea (2.2%) Hypoglycaemia (0.07%) Function liver abnormal (0.01%) |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Diarrhea | 17% Disc. AE |
100 mg 3 times / day multiple, oral (max) Recommended Dose: 100 mg, 3 times / day Route: oral Route: multiple Dose: 100 mg, 3 times / day Sources: |
unhealthy, 57.2 n = 84 Health Status: unhealthy Condition: diabetes mellitus Age Group: 57.2 Sex: M+F Population Size: 84 Sources: |
Flatulence | 26% Disc. AE |
100 mg 3 times / day multiple, oral (max) Recommended Dose: 100 mg, 3 times / day Route: oral Route: multiple Dose: 100 mg, 3 times / day Sources: |
unhealthy, 57.2 n = 84 Health Status: unhealthy Condition: diabetes mellitus Age Group: 57.2 Sex: M+F Population Size: 84 Sources: |
Abdominal pain | 7% Disc. AE |
100 mg 3 times / day multiple, oral (max) Recommended Dose: 100 mg, 3 times / day Route: oral Route: multiple Dose: 100 mg, 3 times / day Sources: |
unhealthy, 57.2 n = 84 Health Status: unhealthy Condition: diabetes mellitus Age Group: 57.2 Sex: M+F Population Size: 84 Sources: |
Burning anal | 1 patient | 300 mg 1 times / day multiple, oral (max) Recommended Dose: 300 mg, 1 times / day Route: oral Route: multiple Dose: 300 mg, 1 times / day Sources: |
unhealthy, 63 n = 1954 Health Status: unhealthy Condition: diabetes mellitus, type 2 Age Group: 63 Sex: M+F Population Size: 1954 Sources: |
Constipation | 1 patient | 300 mg 1 times / day multiple, oral (max) Recommended Dose: 300 mg, 1 times / day Route: oral Route: multiple Dose: 300 mg, 1 times / day Sources: |
unhealthy, 63 n = 1954 Health Status: unhealthy Condition: diabetes mellitus, type 2 Age Group: 63 Sex: M+F Population Size: 1954 Sources: |
Heartburn | 1 patient | 300 mg 1 times / day multiple, oral (max) Recommended Dose: 300 mg, 1 times / day Route: oral Route: multiple Dose: 300 mg, 1 times / day Sources: |
unhealthy, 63 n = 1954 Health Status: unhealthy Condition: diabetes mellitus, type 2 Age Group: 63 Sex: M+F Population Size: 1954 Sources: |
Loose stools | 1 patient | 300 mg 1 times / day multiple, oral (max) Recommended Dose: 300 mg, 1 times / day Route: oral Route: multiple Dose: 300 mg, 1 times / day Sources: |
unhealthy, 63 n = 1954 Health Status: unhealthy Condition: diabetes mellitus, type 2 Age Group: 63 Sex: M+F Population Size: 1954 Sources: |
Weight loss | 1 patient | 300 mg 1 times / day multiple, oral (max) Recommended Dose: 300 mg, 1 times / day Route: oral Route: multiple Dose: 300 mg, 1 times / day Sources: |
unhealthy, 63 n = 1954 Health Status: unhealthy Condition: diabetes mellitus, type 2 Age Group: 63 Sex: M+F Population Size: 1954 Sources: |
Hypoglycaemic episode | 10 patients | 300 mg 1 times / day multiple, oral (max) Recommended Dose: 300 mg, 1 times / day Route: oral Route: multiple Dose: 300 mg, 1 times / day Sources: |
unhealthy, 63 n = 1954 Health Status: unhealthy Condition: diabetes mellitus, type 2 Age Group: 63 Sex: M+F Population Size: 1954 Sources: |
Diarrhea | 13 patients | 300 mg 1 times / day multiple, oral (max) Recommended Dose: 300 mg, 1 times / day Route: oral Route: multiple Dose: 300 mg, 1 times / day Sources: |
unhealthy, 63 n = 1954 Health Status: unhealthy Condition: diabetes mellitus, type 2 Age Group: 63 Sex: M+F Population Size: 1954 Sources: |
Appetite lost | 2 patients | 300 mg 1 times / day multiple, oral (max) Recommended Dose: 300 mg, 1 times / day Route: oral Route: multiple Dose: 300 mg, 1 times / day Sources: |
unhealthy, 63 n = 1954 Health Status: unhealthy Condition: diabetes mellitus, type 2 Age Group: 63 Sex: M+F Population Size: 1954 Sources: |
Nausea | 3 patients | 300 mg 1 times / day multiple, oral (max) Recommended Dose: 300 mg, 1 times / day Route: oral Route: multiple Dose: 300 mg, 1 times / day Sources: |
unhealthy, 63 n = 1954 Health Status: unhealthy Condition: diabetes mellitus, type 2 Age Group: 63 Sex: M+F Population Size: 1954 Sources: |
Abdominal pain | 4 patients | 300 mg 1 times / day multiple, oral (max) Recommended Dose: 300 mg, 1 times / day Route: oral Route: multiple Dose: 300 mg, 1 times / day Sources: |
unhealthy, 63 n = 1954 Health Status: unhealthy Condition: diabetes mellitus, type 2 Age Group: 63 Sex: M+F Population Size: 1954 Sources: |
Flatulence | 68 patients | 300 mg 1 times / day multiple, oral (max) Recommended Dose: 300 mg, 1 times / day Route: oral Route: multiple Dose: 300 mg, 1 times / day Sources: |
unhealthy, 63 n = 1954 Health Status: unhealthy Condition: diabetes mellitus, type 2 Age Group: 63 Sex: M+F Population Size: 1954 Sources: |
Function liver abnormal | 0.01% | 300 mg 1 times / day multiple, oral (max) Recommended Dose: 300 mg, 1 times / day Route: oral Route: multiple Dose: 300 mg, 1 times / day Sources: |
unhealthy, 63 n = 27803 Health Status: unhealthy Condition: diabetes mellitus Age Group: 63 Sex: M+F Population Size: 27803 Sources: |
Hypoglycaemia | 0.07% | 300 mg 1 times / day multiple, oral (max) Recommended Dose: 300 mg, 1 times / day Route: oral Route: multiple Dose: 300 mg, 1 times / day Sources: |
unhealthy, 63 n = 27803 Health Status: unhealthy Condition: diabetes mellitus Age Group: 63 Sex: M+F Population Size: 27803 Sources: |
Flatulence | 13.7% | 300 mg 1 times / day multiple, oral (max) Recommended Dose: 300 mg, 1 times / day Route: oral Route: multiple Dose: 300 mg, 1 times / day Sources: |
unhealthy, 63 n = 27803 Health Status: unhealthy Condition: diabetes mellitus Age Group: 63 Sex: M+F Population Size: 27803 Sources: |
Diarrhoea | 2.2% | 300 mg 1 times / day multiple, oral (max) Recommended Dose: 300 mg, 1 times / day Route: oral Route: multiple Dose: 300 mg, 1 times / day Sources: |
unhealthy, 63 n = 27803 Health Status: unhealthy Condition: diabetes mellitus Age Group: 63 Sex: M+F Population Size: 27803 Sources: |
PubMed
Title | Date | PubMed |
---|---|---|
Altered expression of muscle glucose transporter GLUT-4 in diabetic fatty Zucker rats (ZDF/Drt-fa). | 1991 Dec |
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Effect of acarbose on glucose homeostasis, lipogenesis and lipogenic enzyme gene expression in adipose tissue of weaned rats. | 1993 Jun |
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Acarbose reduces blood pressure in sucrose-induced hypertension in rats. | 1997 Mar |
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Piroxicam and acarbose as chemopreventive agents for spontaneous intestinal adenomas in APC gene 1309 knockout mice. | 1998 Apr |
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Chronic acarbose-feeding increases GLUT1 protein without changing intestinal glucose absorption function. | 2002 Jan 11 |
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Treatment for hyperglycemia promotes pancreatic regeneration in rats without CCK-1 receptor gene expression. | 2003 May |
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Acarbose, an alpha-glucosidase inhibitor, decreases aortic gene expression and serum levels of monocyte chemoattractant protein-1 in fructose-fed rats. | 2006 Sep-Oct |
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Hepatotoxicity caused by both tacrolimus and cyclosporine after living donor liver transplantation. | 2008 Jun |
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Effects of chronic acarbose treatment on adipocyte insulin responsiveness, serum levels of leptin and adiponectin and hypothalamic NPY expression in obese diabetic Wistar rats. | 2008 Mar |
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The alpha-glucosidase inhibitor acarbose prevents obesity and simple steatosis in sequestosome 1/A170/p62 deficient mice. | 2009 May |
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Effects of acarbose on the acceleration of postprandial hyperglycemia-induced pathological changes induced by intermittent hypoxia in lean mice. | 2010 |
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The α-glucosidase inhibitor miglitol decreases glucose fluctuations and inflammatory cytokine gene expression in peripheral leukocytes of Japanese patients with type 2 diabetes mellitus. | 2010 Dec |
Patents
Sample Use Guides
In Vivo Use Guide
Curator's Comment: There is no fixed dosage regimen for the management of diabetes mellitus with PRECOSE or any other pharmacologic agent
Dosage of PRECOSE must be individualized on the basis of both effectiveness and tolerance while not exceeding the maximum recommended dose of 100 mg t.i.d. PRECOSE should be taken three times daily at the start (with the first bite) of each main meal. PRECOSE should be started at a low dose,
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/1618053
Curator's Comment: an inhibition of two thirds of alpha-amylase activity can be expected from pharmacologically used doses of acarbose.
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A10BD17
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ACTIVE MOIETY
METABOLITE ACTIVE (PARENT)