General
Preferred name
LACTULOSE
Synonyms
LACTULOSE HYDRATE ()
Importal ()
D-Lactulose ()
Lactulosum ()
Laxose Orange ()
Laxilose ()
Duphalac ()
Cephulac ()
Lactulose jp17 ()
4-galactosyl fructose ()
Duphalac Dry ()
Bifiteral ()
Constulose ()
Osmolax ()
Evalose ()
Lemlax ()
Constilac ()
Generlac ()
Acilac ()
Heptalac ()
Chronulac ()
Regulose ()
Portalac ()
Enulose ()
NSC-757082 ()
Cholac ()
E966 ()
Lactulose ()
P&D ID
PD001919
CAS
4618-18-2
58166-24-8
29319-45-7
Tags
natural product
drug
available
Drug Status
approved
Max Phase
Phase 4
Drug indication
Laxative
First approval
1976
Structure
Probe scores
P&D probe-likeness score
[[ v.score ]]%
Structure formats
[[ format ]]
[[ compound[format === 'MOL' ? 'molblock' : format.toLowerCase()] ]]
Description
(extracted from source data)
PHARMACODYNAMICS Therapeutically, lactulose has laxative and ammonia-detoxifying actions. [FDA Label] In treating constipation lactulose metabolites draw water into the bowel, causing a cathartic effect through osmotic action.
MOA Lactulose is a synthetic sugar used in the treatment of constipation and liver disease. [FDA Label] 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 intestinal bacteria which results in an increase in osmotic pressure and acidification of the intestinal contents. [T442] This in turn causes an increase in stool water content and softens the stool. In treating hepatic encephalopathy it is thought that lactulose produces trapping of ammonia from the body through the conversion of ammonia entering the intestine to ammonium which is then unable to cross back into systemic circulation. This is followed by lactulose's laxative action encouraging expulsion of the trapped ammonia in the feces.
ROE The primary route of elimination is fecal. [FDA Label] Urinary excretion has been determined to be 3% or less and is essentially complete within 24 hours.
TOXICITY LD50=32.5 g/kg (oral, mouse) [FDA Label] LD50= >20 g/kg (oral, rat) [FDA Label] No human data are available regarding carcinogenicity or impairment of fertility. No animal data are available regarding mutagenecity. [FDA Label] Administration of lactulose solution in the diet of mice for 18 months in concentrations of 3g/100mL and 10g/100mL did not produce any evidence of carcinogenicity. In studies of mice, rats, and rabbits, doses of lactulose up to 4 or 8 g/kg/day produced no adverse effects on fertility.
METABOLISM Lactulose is completely metabolized in the colon by enteric bacteria, and no lactulose is excreted in the feces. [FDA Label] The metabolites produced are organic acids, lactic acid, formic acid, and acetic acid. [T442]
ABSORPTION Lactulose is poorly absorbed from the intestine with very small amounts entering systemic circulation after oral administration. [FDA Label]
HALF-LIFE The data regarding the half-life of lactulose is not readily available or accessible.
ROE 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.[FDA Label] Any unabsorbed lactulose is largely excreted with stool.[FDA Label,L6199,L6202]
PHARMACODYNAMICS Lactulose formulations are most commonly administered via the oral route or the rectal route.[L6202] 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.[FDA Label,L6199,L6202] 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.[FDA Label,L6199,L6202]
MOA Lactulose is a synthetic disaccharide derivative of lactose that consists of one molecule of galactose and one molecule of fructose.[FDA Label,L6199,L6202] 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.[FDA Label,L6199,L6202] 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.[FDA Label,L6199,L6202] 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.[FDA Label,L6199,L6202]; ; 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).[FDA Label,L6199,L6202] 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.[FDA Label,L6199,L6202]. Furthermore, ammonia that diffuses into the acidic colon is ionized to ammonium ions that are incapable of being absorbed back into the blood.[FDA Label,L6199,L6202] These effects, combined with the laxative action of lactulose facilitates the excretion of excess ammonia.[FDA Label,L6199,L6202] 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.[L6202]
INDICATION Lactulose is indicated for use as a laxative in the treatment of chronic constipation in adults and geriatric patients.[FDA Label,L6199,L6202]; ; 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.[FDA Label,L6199,L6202] In particular, lactulose solution has been effective at managing PSE resulting from surgical portacaval shunts or from chronic hepatic diseases like cirrhosis.[L6199]; ; 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 [L6202].
ABSORPTION After administration by the oral route, less than 3% of the given dose of lactulose solution is absorbed by the small intestine.[L6199] 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.[L6199,L6202]
TOXICITY It has been documented that the oral LD50 of lactulose is 48.8 mL/kg in mice and more than 30 mL/ kg in rats.[FDA Label,L6199,L6202]; ; It is expected that overdosage with lactulose would result in abdominal cramps and diarrhea, both of which should be treated with fluid and electrolyte replacement as required.[FDA Label,L6199,L6202]; ; 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.[FDA Label,L6199,L6202] Similarly, it is unknown whether lactulose is distributed into human breastmilk.[FDA Label,L6199,L6202] Use of the medication in nursing women should subsequently be undertaken with caution.[FDA Label,L6199,L6202]; ; Reproduction studies in rats, mice, and rabbits have not revealed any evidence of impaired fertility as a result of administering lactulose.[FDA Label,L6199,L6202]; ; 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.[FDA Label,L6199,L6202]; ; Information regarding the long-term mutagenic potential of lactulose solution in animals or humans and about the long-term carcinogenic potential in humans are not available.[FDA Label,L6199,L6202]
METABOLISM Lactulose is essentially only metabolized in the colon by saccharolytic bacteria that are present there.[FDA Label,L6199,L6202] In particular, the substance is broken down into lactic acid and small amounts of acetic and formic acid.[FDA Label,L6199,L6202] Specific examples of bacteria that normally inhabit the large intestine that are capable of lactulose metabolism include Lactobacilli, Bacteroides, Escherichia coli, and Clostridia.[L6199]
Compound Sets
8
ChEMBL Approved Drugs
CHEMBL296306
ChEMBL Drugs
CHEMBL296306
Drug Repurposing Hub
DrugBank
DB00581
DrugBank Approved Drugs
DB00581
NPC Screening Collection
Other bioactive compounds
The Spectrum Collection
External IDs
55
Properties
(calculated by RDKit )
Molecular Weight
342.12
Hydrogen Bond Acceptors
11
Hydrogen Bond Donors
8
Rotatable Bonds
5
Ring Count
2
Aromatic Ring Count
0
cLogP
-5.4
TPSA
189.53
Fraction CSP3
1.0
Chiral centers
9.0
Largest ring
6.0
QED
0.24
Structural alerts
0
No structural alerts detected
Related compounds
Custom attributes
(extracted from source data)
Indication
portal-systemic encephalopathy (PSE)
MOA
laxative
Source data