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
C[C@H]1O[C@H](O[C@@H]2[C@@H](CO)O[C@H](O[C@H]([C@H](O)CO)[C@H](O)[C@@H](O)C=O)[C@H](O)[C@H]2O)[C@H](O)[C@@H](O)[C@@H]1N[C@H]3C=C(CO)[C@@H](O)[C@H](O)[C@H]3O
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
| Molecular Formula | C25H43NO18 |
| Molecular Weight | 645.6048 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ABSOLUTE |
| Additional Stereochemistry | No |
| Defined Stereocenters | 18 / 18 |
| E/Z Centers | 0 |
| Optical Activity | UNSPECIFIED |
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 |
|---|---|---|---|
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 |
|---|---|---|---|---|
| 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 plasma | Homo sapiens population: HEALTHY age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
AUC
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
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 plasma | Homo sapiens population: HEALTHY age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
|
0.51 μg × h/mL |
300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered: |
ACARBOSE plasma | 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 plasma | Homo sapiens population: HEALTHY age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
Doses
| Dose | Population | Adverse events |
|---|---|---|
100 mg 3 times / day multiple, oral Recommended Dose: 100 mg, 3 times / day Route: oral Route: multiple Dose: 100 mg, 3 times / day Sources: |
unhealthy, 57.2 |
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 Recommended Dose: 300 mg, 1 times / day Route: oral Route: multiple Dose: 300 mg, 1 times / day Sources: |
unhealthy, 63 |
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 Recommended Dose: 300 mg, 1 times / day Route: oral Route: multiple Dose: 300 mg, 1 times / day Sources: |
unhealthy, 63 |
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 Recommended Dose: 100 mg, 3 times / day Route: oral Route: multiple Dose: 100 mg, 3 times / day Sources: |
unhealthy, 57.2 |
| Flatulence | 26% Disc. AE |
100 mg 3 times / day multiple, oral Recommended Dose: 100 mg, 3 times / day Route: oral Route: multiple Dose: 100 mg, 3 times / day Sources: |
unhealthy, 57.2 |
| Abdominal pain | 7% Disc. AE |
100 mg 3 times / day multiple, oral Recommended Dose: 100 mg, 3 times / day Route: oral Route: multiple Dose: 100 mg, 3 times / day Sources: |
unhealthy, 57.2 |
| Burning anal | 1 patient | 300 mg 1 times / day multiple, oral Recommended Dose: 300 mg, 1 times / day Route: oral Route: multiple Dose: 300 mg, 1 times / day Sources: |
unhealthy, 63 |
| Constipation | 1 patient | 300 mg 1 times / day multiple, oral Recommended Dose: 300 mg, 1 times / day Route: oral Route: multiple Dose: 300 mg, 1 times / day Sources: |
unhealthy, 63 |
| Heartburn | 1 patient | 300 mg 1 times / day multiple, oral Recommended Dose: 300 mg, 1 times / day Route: oral Route: multiple Dose: 300 mg, 1 times / day Sources: |
unhealthy, 63 |
| Loose stools | 1 patient | 300 mg 1 times / day multiple, oral Recommended Dose: 300 mg, 1 times / day Route: oral Route: multiple Dose: 300 mg, 1 times / day Sources: |
unhealthy, 63 |
| Weight loss | 1 patient | 300 mg 1 times / day multiple, oral Recommended Dose: 300 mg, 1 times / day Route: oral Route: multiple Dose: 300 mg, 1 times / day Sources: |
unhealthy, 63 |
| Hypoglycaemic episode | 10 patients | 300 mg 1 times / day multiple, oral Recommended Dose: 300 mg, 1 times / day Route: oral Route: multiple Dose: 300 mg, 1 times / day Sources: |
unhealthy, 63 |
| Diarrhea | 13 patients | 300 mg 1 times / day multiple, oral Recommended Dose: 300 mg, 1 times / day Route: oral Route: multiple Dose: 300 mg, 1 times / day Sources: |
unhealthy, 63 |
| Appetite lost | 2 patients | 300 mg 1 times / day multiple, oral Recommended Dose: 300 mg, 1 times / day Route: oral Route: multiple Dose: 300 mg, 1 times / day Sources: |
unhealthy, 63 |
| Nausea | 3 patients | 300 mg 1 times / day multiple, oral Recommended Dose: 300 mg, 1 times / day Route: oral Route: multiple Dose: 300 mg, 1 times / day Sources: |
unhealthy, 63 |
| Abdominal pain | 4 patients | 300 mg 1 times / day multiple, oral Recommended Dose: 300 mg, 1 times / day Route: oral Route: multiple Dose: 300 mg, 1 times / day Sources: |
unhealthy, 63 |
| Flatulence | 68 patients | 300 mg 1 times / day multiple, oral Recommended Dose: 300 mg, 1 times / day Route: oral Route: multiple Dose: 300 mg, 1 times / day Sources: |
unhealthy, 63 |
| Function liver abnormal | 0.01% | 300 mg 1 times / day multiple, oral Recommended Dose: 300 mg, 1 times / day Route: oral Route: multiple Dose: 300 mg, 1 times / day Sources: |
unhealthy, 63 |
| Hypoglycaemia | 0.07% | 300 mg 1 times / day multiple, oral Recommended Dose: 300 mg, 1 times / day Route: oral Route: multiple Dose: 300 mg, 1 times / day Sources: |
unhealthy, 63 |
| Flatulence | 13.7% | 300 mg 1 times / day multiple, oral Recommended Dose: 300 mg, 1 times / day Route: oral Route: multiple Dose: 300 mg, 1 times / day Sources: |
unhealthy, 63 |
| Diarrhoea | 2.2% | 300 mg 1 times / day multiple, oral Recommended Dose: 300 mg, 1 times / day Route: oral Route: multiple Dose: 300 mg, 1 times / day Sources: |
unhealthy, 63 |
PubMed
| Title | Date | PubMed |
|---|---|---|
| The α-glucosidase inhibitor miglitol decreases glucose fluctuations and inflammatory cytokine gene expression in peripheral leukocytes of Japanese patients with type 2 diabetes mellitus. | 2010-12 |
|
| Bioinformatic and biochemical studies point to AAGR-1 as the ortholog of human acid alpha-glucosidase in Caenorhabditis elegans. | 2010-08 |
|
| Effects of acarbose on the acceleration of postprandial hyperglycemia-induced pathological changes induced by intermittent hypoxia in lean mice. | 2010 |
|
| The alpha-glucosidase inhibitor acarbose prevents obesity and simple steatosis in sequestosome 1/A170/p62 deficient mice. | 2009-05 |
|
| Hepatotoxicity caused by both tacrolimus and cyclosporine after living donor liver transplantation. | 2008-06 |
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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. | 2008-03 |
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| Contribution of mucosal maltase-glucoamylase activities to mouse small intestinal starch alpha-glucogenesis. | 2007-07 |
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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. | 2006-12-01 |
|
| Common polymorphisms of the PPAR-gamma2 (Pro12Ala) and PGC-1alpha (Gly482Ser) genes are associated with the conversion from impaired glucose tolerance to type 2 diabetes in the STOP-NIDDM trial. | 2004-12 |
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| [Acarbose-induced acute hepatitis. Report of two events in the same patient]. | 2004-08-25 |
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| Acarbose attenuates experimental non-alcoholic steatohepatitis. | 2004-03-12 |
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| Treatment for hyperglycemia promotes pancreatic regeneration in rats without CCK-1 receptor gene expression. | 2003-05 |
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| Chronic acarbose-feeding increases GLUT1 protein without changing intestinal glucose absorption function. | 2002-01-11 |
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| Piroxicam and acarbose as chemopreventive agents for spontaneous intestinal adenomas in APC gene 1309 knockout mice. | 1998-04 |
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| Acarbose reduces blood pressure in sucrose-induced hypertension in rats. | 1997-03 |
|
| Effect of acarbose on glucose homeostasis, lipogenesis and lipogenic enzyme gene expression in adipose tissue of weaned rats. | 1993-06 |
|
| Altered expression of muscle glucose transporter GLUT-4 in diabetic fatty Zucker rats (ZDF/Drt-fa). | 1991-12 |
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.
Unknown
| Substance Class |
Chemical
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T58MSI464G
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C29711
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| Related Record | Type | Details | ||
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TARGET -> INHIBITOR |
Acarbose acts locally within the gastrointestinal tract, this low systemic bioavailability of parent compound.
IC50
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TARGET->ACTIVATOR OF EXPRESSION |
Acarbose treatment stimulates postprandial GLP-1 secretion in patients with type 2 diabetes. Dependent on dose and saccharide or polysaccharide present. A single dose of 100 mg acarbose during an oral sucrose (disaccharide) load resulted in elevated GLP-1 levels compared to placebo (8, 10, 28, 29) whereas no effect was seen during oral glucose tolerance test (24), emphasizing that acarbose needs relevant carbohydrates to ‘act on’ in order to increase GLP-1 secretion. A single dose of 100 mg acarbose during an oral sucrose (disaccharide) load resulted in elevated GLP-1 levels compared to placebo (8, 10, 28, 29) whereas no effect was seen during oral glucose tolerance test (24), emphasizing that acarbose needs relevant carbohydrates to ‘act on’ in order to increase GLP-1 secretion.
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METABOLITE ACTIVE -> PARENT |
Acarbose is exclusively metabolized within the gastrointestinal tract, principally by intestinal bacteria.
MAJOR
URINE
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IMPURITY -> PARENT |
CHROMATOGRAPHIC PURITY (HPLC/UV)
Ph.Eur.; USP
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IMPURITY -> PARENT |
CHROMATOGRAPHIC PURITY (HPLC/UV)
Ph.Eur.; USP
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IMPURITY -> PARENT |
CHROMATOGRAPHIC PURITY (HPLC/UV)
Ph.Eur.; USP
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IMPURITY -> PARENT |
CHROMATOGRAPHIC PURITY (HPLC/UV)
Ph.Eur.; USP
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IMPURITY -> PARENT |
CHROMATOGRAPHIC PURITY (HPLC/UV)
Other
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IMPURITY -> PARENT |
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
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IMPURITY -> PARENT |
CHROMATOGRAPHIC PURITY (HPLC/UV)
Ph.Eur.; USP
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IMPURITY -> PARENT |
CHROMATOGRAPHIC PURITY (HPLC/UV)
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ACTIVE MOIETY |
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| Name | Property Type | Amount | Referenced Substance | Defining | Parameters | References |
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| Biological Half-life | PHARMACOKINETIC |
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