Investigational Drug Details
| Drug ID: | D198 |
| Drug Name: | Lactulose |
| Synonyms: | 4-O-beta-D-Galactopyranosyl-D-fructofuranose; 4-O-beta-D-Galactopyranosyl-D-fructose; Lactulose |
| Type: | Chemical drug |
| DrugBank ID: | DB00581 |
| DrugBank Description: | 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). Despite being first synthesized in 1929, 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. 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 system, data regarding its optimal place in therapy is often ambiguous. 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. |
| PubChem ID: | 3037557 |
| CasNo: | 4618-18-2 |
| Repositioning for NAFLD: | Yes |
| SMILES: | O([C@@H]([C@@H](C(=O)CO)O)[C@@H](CO)O)[C@@H]1O[C@H](CO)[C@@H]([C@@H]([C@H]1O)O)O |
| Structure: |
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| InChiKey: | PFCRQPBOOFTZGQ-VZXVHDRGSA-N |
| Molecular Weight: | 342.297 |
| DrugBank Targets: | Evolved beta-galactosidase subunit alpha other |
| DrugBank MoA: | Lactulose is a synthetic disaccharide derivative of lactose that consists of one molecule of galactose and one molecule of fructose. 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. 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. 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. 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). 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.. Furthermore, ammonia that diffuses into the acidic colon is ionized to ammonium ions that are incapable of being absorbed back into the blood. These effects, combined with the laxative action of lactulose facilitates the excretion of excess ammonia. 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. |
| DrugBank Pharmacology: | Lactulose formulations are most commonly administered via the oral route or the rectal route. 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. 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. |
| DrugBank Indication: | Lactulose is indicated for use as a laxative in the treatment of chronic constipation in adults and geriatric patients. 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. In particular, lactulose solution has been effective at managing PSE resulting from surgical portacaval shunts or from chronic hepatic diseases like cirrhosis. 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 . |
| Targets: | -- |
| Therapeutic Category: | -- |
| Clinical Trial Progress: | Clinical trial on-going (IRCT2014010715879N3) |
| Latest Progress: | Under clinical trials |
| Trial ID | Source ID | Phases | Status | Study Results | Start Date | Last Update Posted | |
|---|---|---|---|---|---|---|---|
| L0882 | IRCT2014010715879N3 | Not applicable | Not Recruiting | No Results Available | 08/02/2015 | 22 February 2018 | Details |
| L0973 | NCT00808990 | Phase 1 | Not recruiting | No Results Available | 15/12/2008 | 18 April 2016 | Details |
| Strategy ID | Strategy | Synonyms | Related Targets | Related Drugs |
|---|
| Article ID | PMID | Source | Title | |
|---|---|---|---|---|
| A01966 | 34549558 | Adv Clin Exp Med | A novel therapeutic approach to NASH: Both polyethylene glycol 3350 and lactulose reduce hepatic inflammation in C57BL/6J mice. | Details |
| A03776 | 33867442 | Eur J Gastroenterol Hepatol | Small intestinal bacterial overgrowth and orocecal transit time in patients of nonalcoholic fatty liver disease. | Details |
| A05228 | 33331479 | Arq Gastroenterol | PERIPHERAL BLOOD ENDOTOXIN LEVELS ARE NOT ASSOCIATED WITH SMALL INTESTINAL BACTERIAL OVERGROWTH IN NONALCOHOLIC FATTY LIVER DISEASE WITHOUT CIRRHOSIS. | Details |
| A06232 | 32961235 | Life Sci | Liraglutide modulates gut microbiome and attenuates nonalcoholic fatty liver in db/db mice. | Details |
| A07112 | 32618656 | Am J Gastroenterol | Allogenic Fecal Microbiota Transplantation in Patients With Nonalcoholic Fatty Liver Disease Improves Abnormal Small Intestinal Permeability: A Randomized Control Trial. | Details |
| A07485 | 32476788 | World J Gastroenterol | Prognostic significance of hepatic encephalopathy in patients with cirrhosis treated with current standards of care. | Details |
| A07754 | 32363684 | Aliment Pharmacol Ther | Outcomes after hepatic encephalopathy in population-based cohorts of patients with cirrhosis. | Details |
| A08189 | 32213035 | United European Gastroenterol J | Clinical management of type C hepatic encephalopathy. | Details |
| A09183 | 31845776 | Am Fam Physician | Cirrhosis: Diagnosis and Management. | Details |
| A14029 | 29627620 | Contemp Clin Trials | Efficacy, safety, and tolerability of lubiprostone for the treatment of non-alcoholic fatty liver disease in adult patients with constipation: The LUBIPRONE, double-blind, randomised, placebo-controlled study design. | Details |
| A16459 | 28375406 | J Fam Pract | Hot Topics in Primary Care: Diagnosis of Cirrhosis and Evaluation of Hepatic Encephalopathy: Common Errors and Their Significance for the PCP. | Details |
| A18073 | 27367724 | Nutrients | Beneficial Effect of Synbiotic Supplementation on Hepatic Steatosis and Anthropometric Parameters, But Not on Gut Permeability in a Population with Nonalcoholic Steatohepatitis. | Details |
| A18103 | 27350543 | Pediatr Obes | Multiple gut-liver axis abnormalities in children with obesity with and without hepatic involvement. | Details |
| A18939 | 26858714 | Front Microbiol | Ethanol Production by Selected Intestinal Microorganisms and Lactic Acid Bacteria Growing under Different Nutritional Conditions. | Details |
| A22376 | 24631029 | Dig Liver Dis | Intestinal permeability is increased in children with non-alcoholic fatty liver disease, and correlates with liver disease severity. | Details |
| A28210 | 16124065 | World J Gastroenterol | Effect of lactulose on establishment of a rat non-alcoholic steatohepatitis model. | Details |
| A28241 | 15986870 | Dig Dis Sci | Increased orocecal transit time in patients with nonalcoholic fatty liver disease. | Details |
| A29097 | 34567473 | J Community Hosp Intern Med Perspect | Identifying areas of improvement in nursing knowledge regarding hepatic encephalopathy management. | Details |
| A35342 | 21046243 | Dig Dis Sci | Small intestinal bacterial overgrowth in nonalcoholic steatohepatitis: association with toll-like receptor 4 expression and plasma levels of interleukin 8. | Details |
| A36345 | 18397235 | Liver Int | Susceptibility to gut leakiness: a possible mechanism for endotoxaemia in non-alcoholic steatohepatitis. | Details |