- Accession Number
- DB00581 (APRD01063)
- Small Molecule
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)
- Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Constulose Solution 10 g/15mL Oral Actavis Pharma Company 2011-02-28 Not applicable Enulose Solution 10 g/15mL Oral; Rectal Actavis Pharma Company 2011-02-28 Not applicable Generlac Solution 10 g/15mL Oral Morton Grove Pharmaceuticals, Inc. 1996-10-31 Not applicable Kristalose Powder, for solution 20 g/20g Oral Cumberland Pharmaceuticals 2012-01-20 Not applicable Kristalose Powder, for solution 10 g/10g Oral Cumberland Pharmaceuticals 2012-01-20 Not applicable Lactulose Solution 10 g/15mL Oral Roxane Laboratories 1992-05-29 2016-10-13 Lactulose Solution 10 g/15mL Oral Pharmaceutical Associates, Inc. 1966-07-30 Not applicable Lactulose Solution 10 g/15mL Oral Cardinal Health 1996-07-30 Not applicable Lactulose Solution 10 g/15mL Oral Cardinal Health 1966-07-30 Not applicable Lactulose Solution 20 g/30mL Oral Vista Pharm, Inc. 2010-05-10 Not applicable
- Over the Counter Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Apo-lactulose Solution 667 mg Oral Apotex Corporation 2001-02-19 Not applicable Cephulac Syr 667mg/ml Syrup 667 mg Oral Hoechst Marion Roussel 1995-12-31 1998-08-12 Chronulac Syr Syrup 667 mg Oral; Other Merrell Pharms Inc., Division Of Merrell Dow (Can) 1977-12-31 1996-09-09 Chronulac Syr 667mg/ml Syrup 667 mg Oral Hoechst Marion Roussel 1996-12-31 1998-08-12 Comalose R Sirop 10gm/15ml Syrup 10 g Oral; Rectal Rougier Pharma Division Of Ratiopharm Inc 1987-12-31 1999-09-27 Duphalac Powder 95 g Oral Solvay Pharma Inc 1997-11-27 2001-02-12 Duphalac Dry Powder 950 mg Oral Solvay Pharma Inc 1996-07-23 1998-08-04 Gen-lac - Liq 667mg/ml Liquid 667 mg Oral Genpharm Ulc 1990-12-31 2009-08-05 Jamp-lactulose Solution 667 mg Oral Jamp Pharma Corporation 2008-06-20 Not applicable Jamp-lactulose Syrup 667 mg Oral Orbus Pharma Inc 2006-11-07 2010-03-31
- International/Other Brands
- Bifiteral (Abbott) / Cephulac / Cholac (Alra) / Chronulac / Constilac (Alra) / Laevolac (Roche)
- CAS number
- Average: 342.2965
- Chemical Formula
- InChI Key
- IUPAC Name
For the treatment of constipation and hepatic encephalopathy.
- Structured Indications
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.
Target Actions Organism AEvolved beta-galactosidase subunit alphaother Escherichia coli (strain K12)
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
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
- Not Available
LD50=18.2 g/kg (oral, rat). Side effects include diarrhea and resultant dehydration.
- Affected organisms
- Humans and other mammals
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
- Drug Interactions
Drug Interaction Drug group L-Glutamine The therapeutic efficacy of Lactulose can be decreased when used in combination with L-Glutamine. Approved, Investigational, Nutraceutical
- Food Interactions
- Take without regard to meals. Drink liberally.
- 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
- ATC Codes
- A06AD61 — Lactulose, combinations
- A06AD — Osmotically acting laxatives
- A06A — DRUGS FOR CONSTIPATION
- A06 — DRUGS FOR CONSTIPATION
- A — ALIMENTARY TRACT AND METABOLISM
- AHFS Codes
- 40:10.00 — Ammonia Detoxicants
- 56:12.00 — Cathartics and Laxatives
- PDB Entries
- Download (73.6 KB)
- Clinical Trials
- 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
- 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.
- 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
Form Route Strength Syrup Oral 667 mg Syrup Oral; Other 667 mg Syrup Oral; Rectal 10 g Powder Oral 95 g Powder Oral 950 mg Liquid Oral 667 mg Solution Oral 667 mg Powder, for solution Oral 10 g/10g Powder, for solution Oral 20 g/20g Syrup Oral 10 g Liquid Oral; Rectal 10 g/15mL Solution Oral 10 g/15mL Solution Oral 20 g/30mL Solution Oral; Rectal 10 g/15mL Solution Oral 10 g Syrup Oral 3.3 g
Unit description Cost Unit Kristalose 30 20 gm Packets Box 83.93USD box Kristalose 30 10 gm Packets Box 57.57USD box Enulose 10 gm/15ml Solution 473ml Bottle 37.83USD bottle Kristalose 20 gm packet 2.04USD each Kristalose 10 gm packet 1.67USD each Constulose 10 gm/15 ml soln 0.09USD ml Enulose 10 gm/15 ml solution 0.08USD ml Lactulose Encephalopathy 10 gm/15ml Solution 0.08USD ml Lactulose 10 gm/15ml Solution 0.07USD ml Generlac 10 gm/15 ml solution 0.05USD ml Apo-Lactulose 667 mg/ml Syrup 0.02USD ml Jamp-Lactulose 667 mg/ml Syrup 0.02USD ml Pms-Lactulose 667 mg/ml Syrup 0.02USD ml Ratio-Lactulose 667 mg/ml Syrup 0.02USD mlDrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
- Not Available
- Experimental Properties
Property Value Source melting point (°C) 169 °C PhysProp water solubility 7.64E+005 mg/L (at 30 °C) MERCK (1989) logP -4.3 Not Available
- Predicted Properties
Property Value Source Water Solubility 792.0 mg/mL ALOGPS logP -3.3 ALOGPS logP -4.5 ChemAxon logS 0.36 ALOGPS pKa (Strongest Acidic) 10.28 ChemAxon pKa (Strongest Basic) -3 ChemAxon Physiological Charge 0 ChemAxon Hydrogen Acceptor Count 11 ChemAxon Hydrogen Donor Count 8 ChemAxon Polar Surface Area 189.53 Å2 ChemAxon Rotatable Bond Count 5 ChemAxon Refractivity 68.77 m3·mol-1 ChemAxon Polarizability 31.49 Å3 ChemAxon Number of Rings 2 ChemAxon Bioavailability 0 ChemAxon Rule of Five No ChemAxon Ghose Filter No ChemAxon Veber's Rule No ChemAxon MDDR-like Rule No ChemAxon
- 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 inhibitor Non-inhibitor 0.9556 CYP450 2D6 inhibitor Non-inhibitor 0.9386 CYP450 2C19 inhibitor Non-inhibitor 0.9134 CYP450 3A4 inhibitor 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
- Mass Spec (NIST)
- Not Available
Spectrum Spectrum Type Splash Key Predicted GC-MS Spectrum - GC-MS Predicted GC-MS Not Available GC-MS Spectrum - GC-EI-TOF GC-MS splash10-0uxr-0951000000-d976341b4e779d2fcb68 GC-MS Spectrum - GC-EI-TOF GC-MS splash10-0udj-0941000000-e16e35441da7b81d64a1 Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS Not Available
- 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.
- Organic compounds
- Super Class
- Organic oxygen compounds
- 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 alcoholsHydrocarbon derivatives show 1 more
- O-glycosyl compound / Disaccharide / C-glycosyl compound / Oxane / Tetrahydrofuran / Secondary alcohol / Hemiacetal / Oxacycle / Organoheterocyclic compound / PolyolAcetal / Hydrocarbon derivative / Primary alcohol / Alcohol / Aliphatic heteromonocyclic compound show 5 more
- Molecular Framework
- Aliphatic heteromonocyclic compounds
- External Descriptors
- glycosylfructose (CHEBI:6359)
- Escherichia coli (strain K12)
- Pharmacological action
- 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
- Uniprot ID
- Uniprot Name
- Evolved beta-galactosidase subunit alpha
- Molecular Weight
- 117878.225 Da
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- 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]
- 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]
- 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]
- 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 January 14, 2018 10:04