Lactulose

Identification

Name
Lactulose
Accession Number
DB00581  (APRD01063)
Type
Small Molecule
Groups
Approved
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
  • 4-O-beta-D-Galactopyranosyl-D-fructofuranose
  • 4-O-beta-D-Galactopyranosyl-D-fructose
  • Lactulosa
  • Lactulose
  • Lactulosum
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
ConstuloseSolution10 g/15mLOralActavis Pharma Company2011-02-28Not applicableUs
ConstuloseSolution10 g/15mLOralActavis Mid Atlantic LLC,2007-01-032012-02-29Us
EnuloseLiquid10 g/15mLOral; RectalActavis Pharma, LLC1990-10-312012-08-31Us
EnuloseSolution10 g/15mLOral; RectalActavis Pharma Company2011-02-28Not applicableUs
GenerlacSolution10 g/15mLOral; RectalMorton Grove Pharmaceuticals, Inc.1996-10-31Not applicableUs
KristalosePowder, for solution10 g/10gOralCumberland Pharmaceuticals2012-01-20Not applicableUs
KristalosePowder, for solution20 g/20gOralJones Contract Packaging Services2018-01-24Not applicableUs
KristalosePowder, for solution20 g/20gOralCumberland Pharmaceuticals2012-01-20Not applicableUs
KristalosePowder, for solution10 g/10gOralJones Contract Packaging Services2018-01-24Not applicableUs
LactuloseSolution10 g/15mLOralCardinal Health1996-07-302018-09-30Us
Over the Counter Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Apo-lactuloseSolution667 mgOralApotex Corporation2001-02-19Not applicableCanada
Cephulac Syr 667mg/mlSyrup667 mgOralHoechst Marion Roussel1995-12-311998-08-12Canada
Chronulac SyrSyrup667 mgOral; OtherMerrell Pharms Inc., Division Of Merrell Dow (Can)1977-12-311996-09-09Canada
Chronulac Syr 667mg/mlSyrup667 mgOralHoechst Marion Roussel1996-12-311998-08-12Canada
Comalose R Sirop 10gm/15mlSyrup10 gOral; RectalRougier Pharma Division Of Ratiopharm Inc1987-12-311999-09-27Canada
DuphalacPowder95 gOralSolvay Pharma Inc1997-11-272001-02-12Canada
Duphalac DryPowder950 mgOralSolvay Pharma Inc1996-07-231998-08-04Canada
Gen-lac - Liq 667mg/mlLiquid667 mgOralGenpharm Ulc1990-12-312009-08-05Canada
Jamp-lactuloseSolution667 mgOralJamp Pharma Corporation2008-06-20Not applicableCanada
Jamp-lactuloseSyrup667 mgOralOrbus Pharma Inc2006-11-072010-03-31Canada
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
LactuloseLactulose (10 g/15mL)SolutionOral; RectalANI Pharmaceuticals Inc.2008-12-162008-12-16Us
LactuloseLactulose (10 g/15mL)SolutionOralANI Pharmaceuticals Inc.2009-05-212009-05-21Us
International/Other Brands
Bifiteral (Abbott) / Cephulac / Cholac (Alra) / Chronulac / Constilac (Alra) / Laevolac (Roche)
Categories
UNII
9XH2P2N8EP
CAS number
4618-18-2
Weight
Average: 342.2965
Monoisotopic: 342.116211546
Chemical Formula
C12H22O11
InChI Key
JCQLYHFGKNRPGE-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

Pharmacology

Indication

For the treatment of constipation and hepatic encephalopathy.

Associated Conditions
Pharmacodynamics

Therapeutically, 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 action

Lactulose 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.

TargetActionsOrganism
AEvolved beta-galactosidase subunit alpha
other
Escherichia coli (strain K12)
Absorption

Poorly 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 distribution
Not Available
Protein binding
Not Available
Metabolism

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

Route of elimination

The primary route of elimination is fecal. Urinary excretion has been determined to be 3% or less and is essentially complete within 24 hours.

Half life

1.7-2 hours

Clearance
Not Available
Toxicity

LD50=18.2 g/kg (oral, rat). Side effects include diarrhea and resultant dehydration.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(2-benzhydryloxyethyl)diethyl-methylammonium iodideThe therapeutic efficacy of Lactulose can be decreased when used in combination with (2-benzhydryloxyethyl)diethyl-methylammonium iodide.
AcetazolamideThe risk or severity of adverse effects can be increased when Acetazolamide is combined with Lactulose.
AclidiniumThe therapeutic efficacy of Lactulose can be decreased when used in combination with Aclidinium.
AgmatineThe therapeutic efficacy of Lactulose can be decreased when used in combination with Agmatine.
AlfentanilThe therapeutic efficacy of Lactulose can be decreased when used in combination with Alfentanil.
AlmasilateThe therapeutic efficacy of Lactulose can be decreased when used in combination with Almasilate.
AloglutamolThe therapeutic efficacy of Lactulose can be decreased when used in combination with Aloglutamol.
AlphacetylmethadolThe therapeutic efficacy of Lactulose can be decreased when used in combination with Alphacetylmethadol.
AlphaprodineThe therapeutic efficacy of Lactulose can be decreased when used in combination with Alphaprodine.
Aluminium acetoacetateThe therapeutic efficacy of Lactulose can be decreased when used in combination with Aluminium acetoacetate.
Food Interactions
  • Take without regard to meals. Drink liberally.

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 References
Not Available
External Links
Human Metabolome Database
HMDB0000740
KEGG Drug
D00352
KEGG Compound
C07064
PubChem Compound
11333
PubChem Substance
46506757
ChemSpider
10856
BindingDB
50377984
ChEBI
6359
ChEMBL
CHEMBL296306
PharmGKB
PA164748762
HET
W9T
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Lactulose
ATC Codes
A06AD61 — Lactulose, combinationsA06AD11 — Lactulose
AHFS Codes
  • 40:10.00 — Ammonia Detoxicants
  • 56:12.00 — Cathartics and Laxatives
PDB Entries
3w9t
MSDS
Download (73.6 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedBasic ScienceInsulin Resistance / Prediabetic State1
1CompletedTreatmentBowel Evacuant Prior to Colonoscopy1
1CompletedTreatmentOpiate Addiction1
2CompletedPreventionNecrotizing Enterocolitis / Sepsis1
2CompletedTreatmentChronic Constipation1
2CompletedTreatmentFeces, Impacted1
2CompletedTreatmentHepatic Encephalopathy1
2CompletedTreatmentHepatic Encephalopathy / Liver Cirrhosis / Portal Hypertension1
2CompletedTreatmentOccasional Constipation1
2RecruitingTreatmentOvert Hepatic Encephalopathy1
2TerminatedTreatmentMinimal Hepatic Encephalopathy1
2Unknown StatusTreatmentHepatic Encephalopathy1
2, 3CompletedTreatmentAtopic Dermatitis (AD)1
2, 3CompletedTreatmentChronic Liver Diseases (CLD) / Hepatic Encephalopathy1
2, 3RecruitingTreatmentHepatic Encephalopathy1
3CompletedTreatmentChronic Constipation1
3Unknown StatusPreventionEncephalopathy, Hepatocerebral / Hepatic Encephalopathy / Portal-Systemic Encephalopathy1
3WithdrawnTreatmentHepatic Encephalopathy1
4CompletedPreventionHepatic Encephalopathy1
4CompletedTreatmentHepatic Encephalopathy / Liver Cirrhosis1
4CompletedTreatmentHepatic Encephalopathy / Minimal Hepatic Encephalopathy1
4CompletedTreatmentOccasional Constipation2
4RecruitingTreatmentHepatic Encephalopathy1
4RecruitingTreatmentOccasional Constipation1
4RecruitingTreatmentOccasional Constipation / Peritoneal dialysis complication1
4TerminatedTreatmentAnal Fissures / Hemorrhoids1
4TerminatedTreatmentHepatic Encephalopathy / Liver Cirrhosis / Portal Hypertension1
4Unknown StatusNot AvailableHepatic Encephalopathy1
4Unknown StatusTreatmentHepatic Encephalopathy2
4Unknown StatusTreatmentLiver Cirrhosis / Renal Failure1
Not AvailableCompletedDiagnosticHepatic Encephalopathy1
Not AvailableCompletedDiagnosticHepatic Encephalopathy / Liver Cirrhosis1
Not AvailableCompletedPreventionLiver Cirrhosis1
Not AvailableCompletedTreatmentAcute on Chronic Liver Failure With Hepatic Encephalopathy / Acute-On-Chronic Liver Failure1
Not AvailableCompletedTreatmentCirrhosis Related Parkinsonism / Hepatic/Cirrhosis Related Parkinsonism1
Not AvailableCompletedTreatmentHepatic Encephalopathy2
Not AvailableCompletedTreatmentHepatic Encephalopathy / Liver Cirrhosis / Portosystemic Encephalopathy / PSE1
Not AvailableRecruitingTreatmentLiver Cirrhosis1
Not AvailableRecruitingTreatmentRefractory Hepatic Encephalopathy1
Not AvailableUnknown StatusDiagnosticHirschsprung's Disease1
Not AvailableUnknown StatusPreventionHospital Acquired Infections1
Not AvailableUnknown StatusTreatmentAbdominal Pain (AP) / Nausea / Occasional Constipation / Vomiting1
Not AvailableUnknown StatusTreatmentOccasional Constipation1
Not AvailableWithdrawnTreatmentAltered Mental Status / AMS / HE / Hepatic Encephalopathy / Liver Cirrhosis1

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
  • Actavis Group
  • Advanced Pharmaceutical Services Inc.
  • Anip Acquisition Co.
  • Apotex Inc.
  • A-S Medication Solutions LLC
  • Bay Pharma Inc.
  • Cardinal Health
  • Cumberland Pharmaceuticals
  • Diversified Healthcare Services Inc.
  • DPT Laboratories Ltd.
  • Goldline Laboratories Inc.
  • H.J. Harkins Co. Inc.
  • Hi Tech Pharmacal Co. Inc.
  • Infra SRL
  • Innoviant Pharmacy Inc.
  • Ivers Lee Division Of Jones Packaging Inc.
  • Major Pharmaceuticals
  • Merrell Pharmaceuticals Inc.
  • Moeller Pharma GmbH and Co. KG
  • Novex Pharma
  • Palmetto Pharmaceuticals Inc.
  • Pharmaceutical Association
  • Pharmaceutical Packaging Center
  • Physicians Total Care Inc.
  • Precision Dose Inc.
  • Qualitest
  • Ratiopharm Inc.
  • Resolution Chemicals Ltd.
  • Roxane Labs
  • Solvay Pharmaceuticals
  • United Research Laboratories Inc.
  • Vintage Pharmaceuticals Inc.
  • Vistapharm Inc.
  • Watson Pharmaceuticals
  • Wockhardt Ltd.
  • Xactdose Inc.
Dosage forms
FormRouteStrength
SyrupOral667 mg
SyrupOral; Other667 mg
SyrupOral; Rectal10 g
PowderOral95 g
PowderOral950 mg
LiquidOral; Rectal10 g/15mL
LiquidOral667 mg
SolutionOral667 mg
Powder, for solutionOral10 g/10g
Powder, for solutionOral20 g/20g
SyrupOral10 g
SolutionOral10 g/15mL
SolutionOral20 g/30mL
SolutionOral; Rectal10 g/15mL
SolutionOral10 g
SyrupOral3.3 g
Prices
Unit descriptionCostUnit
Kristalose 30 20 gm Packets Box83.93USD box
Kristalose 30 10 gm Packets Box57.57USD box
Enulose 10 gm/15ml Solution 473ml Bottle37.83USD bottle
Kristalose 20 gm packet2.04USD each
Kristalose 10 gm packet1.67USD each
Constulose 10 gm/15 ml soln0.09USD ml
Enulose 10 gm/15 ml solution0.08USD ml
Lactulose Encephalopathy 10 gm/15ml Solution0.08USD ml
Lactulose 10 gm/15ml Solution0.07USD ml
Generlac 10 gm/15 ml solution0.05USD ml
Apo-Lactulose 667 mg/ml Syrup0.02USD ml
Jamp-Lactulose 667 mg/ml Syrup0.02USD ml
Pms-Lactulose 667 mg/ml Syrup0.02USD ml
Ratio-Lactulose 667 mg/ml Syrup0.02USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)169 °CPhysProp
water solubility7.64E+005 mg/L (at 30 °C)MERCK (1989)
logP-4.3Not Available
Predicted Properties
PropertyValueSource
Water Solubility792.0 mg/mLALOGPS
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
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption-0.8407
Blood Brain Barrier+0.6609
Caco-2 permeable-0.8957
P-glycoprotein substrateNon-substrate0.5805
P-glycoprotein inhibitor INon-inhibitor0.8575
P-glycoprotein inhibitor IINon-inhibitor0.9425
Renal organic cation transporterNon-inhibitor0.849
CYP450 2C9 substrateNon-substrate0.8745
CYP450 2D6 substrateNon-substrate0.854
CYP450 3A4 substrateNon-substrate0.6605
CYP450 1A2 substrateNon-inhibitor0.9472
CYP450 2C9 inhibitorNon-inhibitor0.9556
CYP450 2D6 inhibitorNon-inhibitor0.9386
CYP450 2C19 inhibitorNon-inhibitor0.9134
CYP450 3A4 inhibitorNon-inhibitor0.9774
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9619
Ames testNon AMES toxic0.9421
CarcinogenicityNon-carcinogens0.9569
BiodegradationNot ready biodegradable0.6719
Rat acute toxicity1.2563 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9692
hERG inhibition (predictor II)Non-inhibitor0.8684
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
GC-MS Spectrum - GC-EI-TOFGC-MSsplash10-0uxr-0951000000-d976341b4e779d2fcb68
GC-MS Spectrum - GC-EI-TOFGC-MSsplash10-0udj-0941000000-e16e35441da7b81d64a1
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as o-glycosyl compounds. These are glycoside in which a sugar group is bonded through one carbon to another group via a O-glycosidic bond.
Kingdom
Organic compounds
Super Class
Organic oxygen compounds
Class
Organooxygen compounds
Sub Class
Carbohydrates and carbohydrate conjugates
Direct Parent
O-glycosyl compounds
Alternative Parents
Disaccharides / C-glycosyl compounds / Oxanes / Tetrahydrofurans / Secondary alcohols / Hemiacetals / Polyols / Oxacyclic compounds / Acetals / Primary alcohols
show 1 more
Substituents
O-glycosyl compound / Disaccharide / C-glycosyl compound / Oxane / Tetrahydrofuran / Secondary alcohol / Hemiacetal / Oxacycle / Organoheterocyclic compound / Polyol
show 5 more
Molecular Framework
Aliphatic heteromonocyclic compounds
External Descriptors
glycosylfructose (CHEBI:6359)

Targets

Kind
Protein
Organism
Escherichia coli (strain K12)
Pharmacological action
Yes
Actions
Other
General Function
Carbohydrate binding
Specific Function
The wild-type enzyme is an ineffective lactase. Two classes of point mutations dramatically improve activity of the enzyme.
Gene Name
ebgA
Uniprot ID
P06864
Uniprot Name
Evolved beta-galactosidase subunit alpha
Molecular Weight
117878.225 Da
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:17139284]
  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:17016423]
  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:8949640]
  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:97820]
  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:3089818]
  6. Hall BG, Malik HS: Determining the evolutionary potential of a gene. Mol Biol Evol. 1998 Aug;15(8):1055-61. [PubMed:9718732]

Drug created on June 13, 2005 07:24 / Updated on September 18, 2018 23:02