- Accession Number
- DB00581 (APRD01063)
- Small Molecule
Lactulose is a synthetic disaccharide derivative of lactose that is most commonly used as a laxative agent despite also being formally indicated to serve as an adjunct therapy in treating portal-systemic encephalopathy (PSE).Label,3,4 Despite being first synthesized in 19291, investigations regarding its possible use as a laxative for the treatment of chronic constipation did not occur until the 1960s and its first clinical use for treating PSE was not until 1966.4
Nevertheless, although lactulose received formal FDA approval in 1977 and has since become a readily available generic and brand-name non-prescription medication listed on the World Health Organization's List of Essential Medicines as one of the most effective and safe medicines employed in a health system5, data regarding its optimal place in therapy is often ambiguous.4
Especially considering the use of lactulose as a laxative is typically only considered after lifestyle and dietary modifications fail and the fact that lactulose therapy cannot be ethically withheld from patients diagnosed with PSE in a placebo study, the substance may just be one of many options available for treating constipation and its efficacy in managing PSE may never be formally confirmed or refuted via clinical investigation.4
- Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Lactulose Solution 10 g/15mL Oral ANI Pharmaceuticals Inc. 2009-05-21 2009-05-21 Lactulose Solution 10 g/15mL Oral; Rectal ANI Pharmaceuticals Inc. 2008-12-16 2008-12-16
- Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Constulose Solution 10 g/15mL Oral Actavis Mid Atlantic LLC, 2007-01-03 2012-02-29 Constulose Solution 10 g/15mL Oral A-S Medication Solutions 2011-02-28 Not applicable Constulose Solution 10 g/15mL Oral Actavis Pharma, Inc. 2011-02-28 Not applicable Enulose Liquid 10 g/15mL Oral; Rectal Actavis Pharma, LLC 1990-10-31 2012-08-31 Enulose Solution 10 g/15mL Oral; Rectal Actavis Pharma, Inc. 2011-02-28 Not applicable Generlac Solution 10 g/15mL Oral; Rectal Morton Grove Pharmaceuticals, Inc. 1996-10-31 Not applicable Kristalose Powder, for solution 20 g/20g Oral Cumberland Pharmaceuticals Inc. 2012-01-20 Not applicable Kristalose Powder, for solution 10 g/10g Oral Cumberland Pharmaceuticals Inc. 2012-01-20 Not applicable Kristalose Powder, for solution 20 g/20g Oral Jones Contract Packaging Services 2018-01-24 2018-08-20 Kristalose Powder, for solution 10 g/10g Oral Jones Contract Packaging Services 2018-01-24 2018-08-20
- 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
Additionally, lactulose is also employed as an adjunct to protein restriction and supportive therapy for the prevention and treatment of portal-systemic encephalopathy (PSE), including both the hepatic pre-coma and coma variations.Label,3,4 In particular, lactulose solution has been effective at managing PSE resulting from surgical portacaval shunts or from chronic hepatic diseases like cirrhosis.3
Moreover, there have also been studies demonstrating the capacity for lactulose to minimize the formation of gallstones and even some investigations regarding the experimental use of the agent in developing novel anticancer agents owing to its ability to bind galactin carbohydrates involved in various tumor progressions 4.
- Associated Conditions
Lactulose formulations are most commonly administered via the oral route or the rectal route.4 Consequently, because the substance experiences minimal absorption by the gut it typically remains localized in the gastrointestinal tract environment and ultimately demonstrates almost all of its pharmacologic effects within the gut.Label,3,4 In particular, as lactulose elicits its laxative effects in enhancing stool amounts and softening stool, such biochemical and physiologic activities can cause increased bowel sounds (borborygmi), a feeling of bloatedness, belching, frequent flatus, and diarrhea.Label,3,4
- Mechanism of action
Lactulose is a synthetic disaccharide derivative of lactose that consists of one molecule of galactose and one molecule of fructose.Label,3,4 Saccharolytic bacteria present in the large intestine subsequently break the substance down into organic acids like lactic acid and small amounts of formic and acetic acids.Label,3,4 Such resultant volatile fatty acid metabolites, in combination with hydrogen and methane that is also generated consequently enhance intraluminal gas formation, peristaltic gut motility, and elicit an osmotic effect that facilitates an increase in the water content of stool as well as associated stool softening.Label,3,4 All of these actions ultimately assist in facilitating and increasing the frequency of bowel movements in patients experiencing constipation, although it may take 24 to 48 hours after using the medication for this laxative effect to become evident.Label,3,4
At the same time, the formation of such acids via the metabolism of lactulose by colonic bacteria also acidifies the contents of the colon, thereby contributing to the treatment of portal-systemic encephalopathy (PSE).Label,3,4 As one of the principal features of PSE involves the accumulation of nitrogenous waste products like ammonia in the systemic circulation, a state in which the colonic contents become more acidic than blood allows ammonia in the circulation to diffuse into the colon.Label,3,4. Furthermore, ammonia that diffuses into the acidic colon is ionized to ammonium ions that are incapable of being absorbed back into the blood.Label,3,4 These effects, combined with the laxative action of lactulose facilitates the excretion of excess ammonia.Label,3,4 And finally, it is also believed that an acidic colonic environment results in the elimination of urease-producing bacteria that contribute to the formation of ammonia while surviving colonic bacteria use up any trapped ammonia in the colon as a source of nitrogen for protein synthesis.4
Target Actions Organism UEvolved beta-galactosidase subunit alphaother Escherichia coli (strain K12)
After administration by the oral route, less than 3% of the given dose of lactulose solution is absorbed by the small intestine.3 The remaining unabsorbed lactulose reaches the large intestine where it is metabolized - but even then, negligible quantities of unchanged lactulose or its metabolites are absorbed across the colon.3,4
- Volume of distribution
Negligible amounts of lactulose - metabolized or non-metabolized - are absorbed into the body.Label,3,4. Most lactulose that is administered subsequently remains predominantly around the gastrointestinal tract area.
- Protein binding
Negligible amounts of lactulose - metabolized or non-metabolized - are absorbed into the body.Label,3,4. Regardless, data regarding the protein binding of lactulose is not readily available or accessible.
Lactulose is essentially only metabolized in the colon by saccharolytic bacteria that are present there.Label,3,4 In particular, the substance is broken down into lactic acid and small amounts of acetic and formic acid.Label,3,4 Specific examples of bacteria that normally inhabit the large intestine that are capable of lactulose metabolism include Lactobacilli, Bacteroides, Escherichia coli, and Clostridia.3
- Route of elimination
The renal excretion of any lactulose that manages to be absorbed into the circulation has been determined to be 3% or less and is generally complete within 24 hours.Label Any unabsorbed lactulose is largely excreted with stool.Label,3,4
- Half life
The data regarding the half-life of lactulose is not readily available or accessible.
Considering the use of lactulose during pregnancy in humans has not been formally investigated, the agent should only be used during pregnancy only when clearly needed.Label,3,4 Similarly, it is unknown whether lactulose is distributed into human breastmilk.Label,3,4 Use of the medication in nursing women should subsequently be undertaken with caution.Label,3,4
Data regarding the safety and efficacy of using lactulose in children for the treatment of chronic constipation or portal-systemic encephalopathy (PSE) is either very limited or yet to be established.Label,3,4
- Affected organisms
- Humans and other mammals
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Comprehensive structured data on known drug adverse effects with statistical prevalence. MedDRA and ICD10 ids are provided for adverse effect conditions and symptoms.Learn more
Structured data covering drug contraindications. Each contraindication describes a scenario in which the drug is not to be used. Includes restrictions on co-administration, contraindicated populations, and more.Learn more
Structured data representing warnings from the black box section of drug labels. These warnings cover important and dangerous risks, contraindications, or adverse effects.Learn more
- Drug Interactions
Drug Interaction (R)-warfarin The risk or severity of bleeding can be increased when Lactulose is combined with (R)-warfarin. (S)-Warfarin The risk or severity of bleeding can be increased when Lactulose is combined with (S)-Warfarin. 6-Deoxyerythronolide B The therapeutic efficacy of Lactulose can be decreased when used in combination with 6-Deoxyerythronolide B. Acenocoumarol The risk or severity of bleeding can be increased when Lactulose is combined with Acenocoumarol. Acetazolamide The risk or severity of adverse effects can be increased when Acetazolamide is combined with Lactulose. Acetyl sulfisoxazole The therapeutic efficacy of Lactulose can be decreased when used in combination with Acetyl sulfisoxazole. Aclidinium The therapeutic efficacy of Lactulose can be decreased when used in combination with Aclidinium. Agmatine The therapeutic efficacy of Lactulose can be decreased when used in combination with Agmatine. Alcuronium The therapeutic efficacy of Lactulose can be decreased when used in combination with Alcuronium. Alfentanil The therapeutic efficacy of Lactulose can be decreased when used in combination with Alfentanil.Additional Data Available
- Extended DescriptionExtended Description
Extended description of the mechanism of action and particular properties of each drug interaction.Learn more
A severity rating for each drug interaction, from minor to major.Learn more
- Evidence LevelEvidence Level
A rating for the strength of the evidence supporting each drug interaction.Learn more
- ActionEvidence Level
An effect category for each drug interaction. Know how this interaction affects the subject drug.Learn more
- 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
- Schumann C: Medical, nutritional and technological properties of lactulose. An update. Eur J Nutr. 2002 Nov;41 Suppl 1:I17-25. doi: 10.1007/s00394-002-1103-6. [PubMed:12420112]
- Canadian Pharmacists Association (2019). Compendium of Pharmaceuticals and Specialties. Canadian Pharmacists Association.
- Lactulose Canadian Product Monograph [Link]
- NCBI StatPearls [Internet]: Lactulose [Link]
- WHO Model List of Essential Medicines 19th List (April 2015 - Amended November 2015) [Link]
- 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
- 3w9t / 6b8k / 6b94
- FDA label
- Download (151 KB)
- 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; Rectal 10 g/15mL 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 Solution Oral 10 g/15mL Solution Oral 10 g/10g 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 http://www.hmdb.ca/metabolites/HMDB0000740 water solubility Soluble in cold water, hot water. Solubility in water: 76.4% @ 30 deg. C MSDS logP -4.3 http://www.hmdb.ca/metabolites/HMDB0000740
- 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
- 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]
- 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]
- 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 May 21, 2019 12:07