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Identification
NameAcarbose
Accession NumberDB00284  (APRD00656)
TypeSmall Molecule
GroupsApproved, Investigational
Description

An inhibitor of alpha glucosidase that retards the digestion and absorption of carbohydrates in the small intestine and hence reduces the increase in blood-glucose concentrations after a carbohydrate load. It is given orally to non-insulin dependent diabetes mellitus patients where diet modification or oral hypoglycemic agents do not control their condition. (From Martindale The Extra Pharmacopoeia, 31st ed)

Structure
Thumb
Synonyms
SynonymLanguageCode
AcarbosaNot AvailableNot Available
AcarboseNot AvailableNot Available
AcarbosumNot AvailableNot Available
GlucobayNot AvailableNot Available
PrecoseNot AvailableNot Available
SaltsNot Available
Brand names
NameCompany
GlucobayBayer AG
PrandaseBayer AG
PrecoseBayer Pharmaceuticals
Brand mixturesNot Available
CategoriesNot Available
CAS number56180-94-0
WeightAverage: 645.6048
Monoisotopic: 645.248013577
Chemical FormulaC25H43NO18
InChI KeyXUFXOAAUWZOOIT-JMPDRRIHSA-N
InChI
InChI=1S/C25H43NO18/c1-6-11(26-8-2-7(3-27)12(30)15(33)13(8)31)14(32)19(37)24(40-6)43-22-10(5-29)42-25(20(38)17(22)35)44-21-9(4-28)41-23(39)18(36)16(21)34/h2,6,8-39H,3-5H2,1H3/t6-,8+,9-,10-,11-,12+,13+,14+,15+,16-,17-,18-,19-,20-,21-,22-,23-,24-,25-/m1/s1
IUPAC Name
(2R,3R,4R,5S,6R)-5-{[(2R,3R,4R,5S,6R)-5-{[(2R,3R,4S,5S,6R)-3,4-dihydroxy-6-methyl-5-{[(1S,4S,5S,6S)-4,5,6-trihydroxy-3-(hydroxymethyl)cyclohex-2-en-1-yl]amino}oxan-2-yl]oxy}-3,4-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy}-6-(hydroxymethyl)oxane-2,3,4-triol
SMILES
C[C@H]1O[C@H](O[C@@H]2[C@@H](CO)O[C@H](O[C@@H]3[C@@H](CO)O[C@@H](O)[C@H](O)[C@H]3O)[C@H](O)[C@H]2O)[C@H](O)[C@@H](O)[C@@H]1N[C@H]1C=C(CO)[C@H](O)[C@H](O)[C@H]1O
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassOrganooxygen Compounds
ClassCarbohydrates and Carbohydrate Conjugates
SubclassTetrasaccharides
Direct parentTetrahexoses
Alternative parentsO-glycosyl Compounds; Amino Sugars; Aminocyclitols and Derivatives; Oxanes; 1,2-Aminoalcohols; 1,2-Diols; Secondary Alcohols; Hemiacetals; Dialkylamines; Polyamines; Primary Alcohols; Acetals
Substituentso-glycosyl compound; glycosyl compound; glucosamine; amino sugar; aminocyclitol derivative; cyclitol derivative; oxane; polyol; 1,2-diol; secondary alcohol; hemiacetal; 1,2-aminoalcohol; primary alcohol; polyamine; ether; acetal; secondary aliphatic amine; secondary amine; alcohol; amine; organonitrogen compound
Classification descriptionThis compound belongs to the tetrahexoses. These are tetrasaccharides containing four hexose carbohydrates.
Pharmacology
IndicationFor treatment and management of diabetes type II (used in combination therapy as a second or third line agent)
PharmacodynamicsUsed to reduce blood gluose in patients with type 2 diabetes. Acarbose is a complex oligosaccharide that delays the digestion of ingested carbohydrates, thereby resulting in a smaller rise in blood glucose concentration following meals. Acarbose binds to and inhibits alpha amylase and alpha-gluocside hydrolases. In diabetic patients, this enzyme inhibition results in a delayed glucose absorption and a lowering of postprandial hyperglycemia.
Mechanism of actionAcarbose reversibly bind to pancreatic alpha-amylase and membrane-bound intestinal alpha-glucoside hydrolases. These enzymes inhibit hydrolysis of complex starches to oligosaccharides in the lumen of the small intestine and hydrolysis of oligosaccharides, trisaccharides, and disaccharides to glucose and other monosaccharides in the brush border of the small intestine.
AbsorptionExtremely low bioavailability. Less than 2% of an oral dose of acarbose was absorbed as active drug. Peak plasma concentrations of the active drug were achieved 1 hour after dosing. Drug accumulation does not occur with multiple doses.
Volume of distributionNot Available
Protein bindingNot Available
Metabolism

Acarbose is only metabolized within the gastrointestinal tract by intestinal bacteria and also digestive enzymes to a lesser extent. 4-methylpyrogallol derivatives (sulfate, methyl, and glucuronide conjugates) are the major metabolites. One metabolite (formed by cleavage of a glucose molecule from acarbose) also has alpha-glucosidase inhibitory activity.

Route of eliminationThe fraction of acarbose that is absorbed as intact drug is almost completely excreted by the kidneys. A fraction of the metabolites (approximately 34% of the dose) was absorbed and subsequently excreted in the urine. The active metabolite is excreted into the urine and accounts for less than 2% of the total administered dose. When given intravenously, 89% of the dose was excreted into the urine as the active drug. When given orally, less than 2% of the oral dose was recovered into the urine as active (parent compound and active metabolite) drug.
Half lifeHealthy volunteers = 2 hours
ClearanceNot Available
ToxicityGastrointestinal symptoms are the most common reactions to acarbose.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption - 0.8467
Blood Brain Barrier - 0.9723
Caco-2 permeable - 0.725
P-glycoprotein substrate Substrate 0.5316
P-glycoprotein inhibitor I Inhibitor 0.5421
P-glycoprotein inhibitor II Non-inhibitor 0.8656
Renal organic cation transporter Non-inhibitor 0.8647
CYP450 2C9 substrate Non-substrate 0.7581
CYP450 2D6 substrate Non-substrate 0.8505
CYP450 3A4 substrate Non-substrate 0.5683
CYP450 1A2 substrate Non-inhibitor 0.8791
CYP450 2C9 substrate Non-inhibitor 0.8677
CYP450 2D6 substrate Non-inhibitor 0.8974
CYP450 2C19 substrate Non-inhibitor 0.8392
CYP450 3A4 substrate Non-inhibitor 0.986
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.7163
Ames test Non AMES toxic 0.8054
Carcinogenicity Non-carcinogens 0.967
Biodegradation Not ready biodegradable 0.6447
Rat acute toxicity 1.4610 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.8586
hERG inhibition (predictor II) Non-inhibitor 0.8288
Pharmacoeconomics
Manufacturers
  • Impax laboratories inc
  • Roxane laboratories inc
  • Watson laboratories inc
  • Bayer healthcare pharmaceuticals inc
Packagers
Dosage forms
FormRouteStrength
TabletOral25 mg, 50 mg, 100 mg
Prices
Unit descriptionCostUnit
Acarbose 100 100 mg tablet Bottle120.62USDbottle
Acarbose 100 50 mg tablet Bottle100.71USDbottle
Acarbose 100 25 mg tablet Bottle93.54USDbottle
Precose 100 mg tablet1.28USDtablet
Acarbose 100 mg tablet1.17USDtablet
Precose 50 mg tablet1.11USDtablet
Precose 25 mg tablet1.01USDtablet
Acarbose 25 mg tablet0.91USDtablet
Acarbose 50 mg tablet0.88USDtablet
Glucobay 100 mg Tablet0.4USDtablet
Glucobay 50 mg Tablet0.29USDtablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
logP-6.8Not Available
Predicted Properties
PropertyValueSource
Water Solubility148.0ALOGPS
logP-2.7ALOGPS
logP-7.6ChemAxon
logS-0.64ALOGPS
pKa (Strongest Acidic)11.23ChemAxon
pKa (Strongest Basic)7.03ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count19ChemAxon
Hydrogen Donor Count14ChemAxon
Polar Surface Area321.17 Å2ChemAxon
Rotatable Bond Count9ChemAxon
Refractivity137.6 m3·mol-1ChemAxon
Polarizability62.39 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Spectra
SpectraNot Available
References
Synthesis Reference

Anneliese Crueger, Wolfgang Piepersberg, Jurgen Distler, Ansgar Stratmann, “Acarbose biosynthesis genes from actinoplanes sp., process for the isolation thereof and the use thereof.” U.S. Patent US5753501, issued December, 1977.

US5753501
General Reference
  1. Clissold SP, Edwards C: Acarbose. A preliminary review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential. Drugs. 1988 Mar;35(3):214-43. Pubmed
  2. FDA label
External Links
ResourceLink
KEGG DrugD00216
KEGG CompoundC06802
PubChem Compound441184
PubChem Substance46508248
ChemSpider389971
ChEBI2376
ChEMBLCHEMBL1566
Therapeutic Targets DatabaseDCL000309
PharmGKBPA448010
Drug Product Database2190893
RxListhttp://www.rxlist.com/cgi/generic/acarbose.htm
Drugs.comhttp://www.drugs.com/cdi/acarbose.html
WikipediaAcarbose
ATC CodesA10BF01
AHFS Codes
  • 68:20.02
PDB EntriesNot Available
FDA labelshow(268 KB)
MSDSNot Available
Interactions
Drug Interactions
Drug
DigoxinAcarbose may decrease the serum levels of digoin. It is thought that acarbose reduces digoin absorption. Monitor for changes in digoxin serum levels and therapeutic and adverse effects if acarbose is initiated, discontinued or dose changed.
Somatropin recombinantSomatropin may antagonize the hypoglycemic effect of acarbose. Monitor for changes in fasting and postprandial blood sugars.
Food Interactions
  • Take with food, at beginning of each meal.

Targets

1. Maltase-glucoamylase, intestinal

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Maltase-glucoamylase, intestinal O43451 Details

References:

  1. Okumiya T, Keulemans JL, Kroos MA, Van der Beek NM, Boer MA, Takeuchi H, Van Diggelen OP, Reuser AJ: A new diagnostic assay for glycogen storage disease type II in mixed leukocytes. Mol Genet Metab. 2006 May;88(1):22-8. Epub 2005 Dec 15. Pubmed
  2. Zhang H, Kallwass H, Young SP, Carr C, Dai J, Kishnani PS, Millington DS, Keutzer J, Chen YT, Bali D: Comparison of maltose and acarbose as inhibitors of maltase-glucoamylase activity in assaying acid alpha-glucosidase activity in dried blood spots for the diagnosis of infantile Pompe disease. Genet Med. 2006 May;8(5):302-6. Pubmed
  3. Gelb MH, Turecek F, Scott CR, Chamoles NA: Direct multiplex assay of enzymes in dried blood spots by tandem mass spectrometry for the newborn screening of lysosomal storage disorders. J Inherit Metab Dis. 2006 Apr-Jun;29(2-3):397-404. Pubmed
  4. Yamagishi S, Matsui T, Ueda S, Fukami K, Okuda S: Clinical utility of acarbose, an alpha-glucosidase inhibitor in cardiometabolic disorders. Curr Drug Metab. 2009 Feb;10(2):159-63. Pubmed
  5. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

2. Pancreatic alpha-amylase

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Pancreatic alpha-amylase P04746 Details

References:

  1. Jonas L, Mikkat U, Lehmann R, Schareck W, Walzel H, Schroder W, Lopp H, Pussa T, Toomik P: Inhibitory effects of human and porcine alpha-amylase on CCK-8-stimulated lipase secretion of isolated rat pancreatic acini. Pancreatology. 2003;3(4):342-8. Pubmed

3. Lysosomal alpha-glucosidase

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Lysosomal alpha-glucosidase P10253 Details

References:

  1. Salehi A, Fan BG, Ekelund M, Nordin G, Lundquist I: TPN-evoked dysfunction of islet lysosomal activity mediates impairment of glucose-stimulated insulin release. Am J Physiol Endocrinol Metab. 2001 Jul;281(1):E171-9. Pubmed
  2. Li Y, Scott CR, Chamoles NA, Ghavami A, Pinto BM, Turecek F, Gelb MH: Direct multiplex assay of lysosomal enzymes in dried blood spots for newborn screening. Clin Chem. 2004 Oct;50(10):1785-96. Epub 2004 Aug 3. Pubmed
  3. Lundquist I, Panagiotidis G: The relationship of islet amyloglucosidase activity and glucose-induced insulin secretion. Pancreas. 1992;7(3):352-7. Pubmed
  4. Zhang H, Kallwass H, Young SP, Carr C, Dai J, Kishnani PS, Millington DS, Keutzer J, Chen YT, Bali D: Comparison of maltose and acarbose as inhibitors of maltase-glucoamylase activity in assaying acid alpha-glucosidase activity in dried blood spots for the diagnosis of infantile Pompe disease. Genet Med. 2006 May;8(5):302-6. Pubmed
  5. Gelb MH, Turecek F, Scott CR, Chamoles NA: Direct multiplex assay of enzymes in dried blood spots by tandem mass spectrometry for the newborn screening of lysosomal storage disorders. J Inherit Metab Dis. 2006 Apr-Jun;29(2-3):397-404. Pubmed
  6. Lullmann-Rauch R, Watermann D: Fusion of storage lysosomes in experimental lipidosis and glycogenosis. Exp Mol Pathol. 1987 Feb;46(1):136-43. Pubmed
  7. Bourbon JR, Doucet E, Rieutort M: Role of alpha-glucosidase in fetal lung maturation. Biochim Biophys Acta. 1987 Jan 13;917(1):203-10. Pubmed
  8. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

4. Sucrase-isomaltase, intestinal

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Sucrase-isomaltase, intestinal P14410 Details

References:

  1. Juretic D, Bernik S, Cop L, Hadzija M, Petlevski R, Lukac-Bajalo J: Short-term effect of acarbose on specific intestinal disaccharidase activities and hyperglycaemia in CBA diabetic mice. J Anim Physiol Anim Nutr (Berl). 2003 Aug;87(7-8):263-8. Pubmed
  2. Meyer H, Wieczorek H, Zeiske W: K+ transport in the caterpillar intestine epithelium: role of osmolytes for the K+-secretory capacity of the tobacco hornworm midgut. J Comp Physiol [B]. 2004 Oct;174(7):527-39. Epub 2004 Aug 20. Pubmed
  3. Karley AJ, Ashford DA, Minto LM, Pritchard J, Douglas AE: The significance of gut sucrase activity for osmoregulation in the pea aphid, Acyrthosiphon pisum. J Insect Physiol. 2005 Dec;51(12):1313-9. Epub 2005 Sep 15. Pubmed
  4. Samulitis BK, Goda T, Lee SM, Koldovsky O: Inhibitory mechanism of acarbose and 1-deoxynojirimycin derivatives on carbohydrases in rat small intestine. Drugs Exp Clin Res. 1987;13(8):517-24. Pubmed
  5. Newbrun E, Hoover CI, Walker GJ: Inhibition by acarbose, nojirimycin and 1-deoxynojirimycin of glucosyltransferase produced by oral streptococci. Arch Oral Biol. 1983;28(6):531-6. Pubmed

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Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:09