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Identification
NameLactulose
Accession NumberDB00581  (APRD01063)
TypeSmall Molecule
GroupsApproved
Description

A synthetic disaccharide used in the treatment of constipation and hepatic encephalopathy. It has also been used in the diagnosis of gastrointestinal disorders. (From Martindale, The Extra Pharmacopoeia, 30th ed, p887)

Structure
Thumb
Synonyms
SynonymLanguageCode
4-O-beta-D-Galactopyranosyl-D-fructofuranoseNot AvailableNot Available
4-O-beta-D-Galactopyranosyl-D-fructoseNot AvailableNot Available
LactulosaSpanishINN
LactuloseNot AvailableINN, BAN, USAN, JAN
LactulosumLatinINN
SaltsNot Available
Brand names
NameCompany
BifiteralAbbott
CephulacNot Available
CholacAlra
ChronulacNot Available
ConstilacAlra
ConstuloseActavis
DuphalacAbbott
EnuloseActavis
GenerlacMorton Grove
KristaloseNot Available
LaevolacRoche
Brand mixturesNot Available
Categories
CAS number4618-18-2
WeightAverage: 342.2965
Monoisotopic: 342.116211546
Chemical FormulaC12H22O11
InChI KeyJCQLYHFGKNRPGE-FCVZTGTOSA-N
InChI
InChI=1S/C12H22O11/c13-1-4-6(16)7(17)8(18)11(21-4)22-9-5(2-14)23-12(20,3-15)10(9)19/h4-11,13-20H,1-3H2/t4-,5-,6+,7+,8-,9-,10+,11+,12-/m1/s1
IUPAC Name
(2S,3R,4S,5R,6R)-2-{[(2R,3S,4S,5R)-4,5-dihydroxy-2,5-bis(hydroxymethyl)oxolan-3-yl]oxy}-6-(hydroxymethyl)oxane-3,4,5-triol
SMILES
OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassOrganooxygen Compounds
ClassCarbohydrates and Carbohydrate Conjugates
SubclassDisaccharides
Direct parentMixed Pentose/Hexose Disaccharides
Alternative parentsO-glycosyl Compounds; C-glycosyl Compounds; Oxanes; Tetrahydrofurans; Oxolanes; Hemiacetals; 1,2-Diols; Secondary Alcohols; Polyamines; Acetals; Primary Alcohols
Substituentsglycosyl compound; o-glycosyl compound; c-glycosyl compound; oxane; oxolane; tetrahydrofuran; secondary alcohol; polyol; 1,2-diol; hemiacetal; ether; primary alcohol; polyamine; acetal; alcohol
Classification descriptionThis compound belongs to the mixed pentose/hexose disaccharides. These are disaccharides containing both an hexose and a pentose.
Pharmacology
IndicationFor the treatment of constipation and hepatic encephalopathy.
PharmacodynamicsTherapeutically, lactulose has laxative and ammonia-detoxifying actions. In treating constipation lactulose metabolites draw water into the bowel, causing a cathartic effect through osmotic action.
Mechanism of actionLactulose is a synthetic sugar used in the treatment of constipation and liver disease. It consists of the monosaccharides fructose and galactose. In the colon, lactulose is broken down primarily to lactic acid, and also to small amounts of formic and acetic acids, by the action of via evolved-beta galactosidase from colonic bacteria, which results in an increase in osmotic pressure and slight acidification of the colonic contents. This in turn causes an increase in stool water content and softens the stool. In treating heptic diseases (hepatic encephalopathy) it is thought that lactulose draws out ammonia from the body in the same way that it draws out water into the colon.
AbsorptionPoorly absorbed from the gastrointestinal tract as no human enzyme that is capable of hydrolysis of this disaccharide is present in human gastrointestinal tissue.
Volume of distributionNot Available
Protein bindingNot Available
Metabolism

Lactulose is completely metabolized in the colon by enteric bacteria, and no lactulose is excreted in the feces.

Route of eliminationThe primary route of elimination is fecal. Urinary excretion has been determined to be 3% or less and is essentially complete within 24 hours.
Half life1.7-2 hours
ClearanceNot Available
ToxicityLD50=18.2 g/kg (oral, rat). Side effects include diarrhea and resultant dehydration.
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 - 0.8407
Blood Brain Barrier + 0.6609
Caco-2 permeable - 0.8957
P-glycoprotein substrate Non-substrate 0.5805
P-glycoprotein inhibitor I Non-inhibitor 0.8575
P-glycoprotein inhibitor II Non-inhibitor 0.9425
Renal organic cation transporter Non-inhibitor 0.849
CYP450 2C9 substrate Non-substrate 0.8745
CYP450 2D6 substrate Non-substrate 0.854
CYP450 3A4 substrate Non-substrate 0.6605
CYP450 1A2 substrate Non-inhibitor 0.9472
CYP450 2C9 substrate Non-inhibitor 0.9556
CYP450 2D6 substrate Non-inhibitor 0.9386
CYP450 2C19 substrate Non-inhibitor 0.9134
CYP450 3A4 substrate Non-inhibitor 0.9774
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9619
Ames test Non AMES toxic 0.9421
Carcinogenicity Non-carcinogens 0.9569
Biodegradation Not ready biodegradable 0.6719
Rat acute toxicity 1.2563 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9692
hERG inhibition (predictor II) Non-inhibitor 0.8684
Pharmacoeconomics
Manufacturers
  • Inalco spa
  • Sanofi aventis us llc
  • Alra laboratories inc
  • Actavis mid atlantic llc
  • Solvay pharmaceuticals
  • Teva pharmaceuticals usa
  • Ani pharmaceuticals inc
  • Hi tech pharmacal co inc
  • Morton grove pharmaceuticals inc
  • Novex pharma
  • Paco pharmaceutical services inc
  • Pharmaceutical assoc inc div beach products
  • Roxane laboratories inc
  • Vintage pharmaceuticals inc
  • Vistapharm inc
  • Nostrum laboratories inc
Packagers
Dosage forms
FormRouteStrength
LiquidOral
SolutionOral
SyrupOral
Prices
Unit descriptionCostUnit
Kristalose 30 20 gm Packets Box83.93USDbox
Kristalose 30 10 gm Packets Box57.57USDbox
Enulose 10 gm/15ml Solution 473ml Bottle37.83USDbottle
Kristalose 20 gm packet2.04USDeach
Kristalose 10 gm packet1.67USDeach
Constulose 10 gm/15 ml soln0.09USDml
Enulose 10 gm/15 ml solution0.08USDml
Lactulose Encephalopathy 10 gm/15ml Solution0.08USDml
Lactulose 10 gm/15ml Solution0.07USDml
Generlac 10 gm/15 ml solution0.05USDml
Apo-Lactulose 667 mg/ml Syrup0.02USDml
Jamp-Lactulose 667 mg/ml Syrup0.02USDml
Pms-Lactulose 667 mg/ml Syrup0.02USDml
Ratio-Lactulose 667 mg/ml Syrup0.02USDml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point169 °CPhysProp
water solubility7.64E+005 mg/L (at 30 °C)MERCK (1989)
logP-4.3Not Available
Predicted Properties
PropertyValueSource
Water Solubility792.0ALOGPS
logP-3.3ALOGPS
logP-4.5ChemAxon
logS0.36ALOGPS
pKa (Strongest Acidic)10.28ChemAxon
pKa (Strongest Basic)-3ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count11ChemAxon
Hydrogen Donor Count8ChemAxon
Polar Surface Area189.53 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity68.77 m3·mol-1ChemAxon
Polarizability31.49 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis Reference

Renato Carobbi, Franco Innocenti, “Process for preparing high-purity lactulose syrup and the syrup obtained.” U.S. Patent US4978397, issued April, 1961.

US4978397
General ReferenceNot Available
External Links
ResourceLink
KEGG DrugD00352
KEGG CompoundC07064
PubChem Compound11333
PubChem Substance46506757
ChemSpider10856
ChEBI6359
ChEMBLCHEMBL296306
PharmGKBPA164748762
Drug Product Database690686
RxListhttp://www.rxlist.com/cgi/generic2/lactulose.htm
Drugs.comhttp://www.drugs.com/cdi/lactulose-crystals.html
PDRhealthhttp://www.pdrhealth.com/drug_info/nmdrugprofiles/nutsupdrugs/lac_0300.shtml
WikipediaLactulose
ATC CodesA06AD11
AHFS Codes
  • 40:10.00
PDB EntriesNot Available
FDA labelNot Available
MSDSshow(73.6 KB)
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

1. Evolved beta-galactosidase subunit alpha

Kind: protein

Organism: Escherichia coli (strain K12)

Pharmacological action: yes

Actions: other

Components

Name UniProt ID Details
Evolved beta-galactosidase subunit alpha P06864 Details

References:

  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Bjarnason I, Batt R, Catt S, Macpherson A, Maxton D, Menzies IS: Evaluation of differential disaccharide excretion in urine for non-invasive investigation of altered intestinal disaccharidase activity caused by alpha-glucosidase inhibition, primary hypolactasia, and coeliac disease. Gut. 1996 Sep;39(3):374-81. Pubmed
  4. Cook GC: Breath hydrogen concentrations after oral lactose and lactulose in tropical malabsorption and adult hypolactasia. Trans R Soc Trop Med Hyg. 1978;72(3):277-81. Pubmed
  5. Noone C, Menzies IS, Banatvala JE, Scopes JW: Intestinal permeability and lactose hydrolysis in human rotaviral gastroenteritis assessed simultaneously by non-invasive differential sugar permeation. Eur J Clin Invest. 1986 Jun;16(3):217-25. Pubmed
  6. Hall BG, Malik HS: Determining the evolutionary potential of a gene. Mol Biol Evol. 1998 Aug;15(8):1055-61. Pubmed

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Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:11