Erosive Esophagitis(EE)

Also known as: Erosive Esophagitis / Erosive oesophagitis

DrugDrug NameDrug Description
DB05351DexlansoprazoleDexlansoprazole is a new generation proton pump inhibitor (PPI) used for the management of symptoms associated with gastroesophageal reflux disease (GERD) and erosive esophagitis. Dexlansoprazole is the R-enantiomer of [DB00448], which is composed of a racemic mixture of the R- and S-enantiomers. Compared to the older generation of PPIs (which includes [DB00213], [DB00338], and [DB00448]) [A178084], dexlansoprazole MR has a unique pharmacokinetic profile due to its delayed-release and dual-delivery release system. The active ingredient is released in two phases at different pH values and at different time points, resulting in two peak concentrations in the blood; 25% of the dose is released at pH 5.5 in the proximal duodenum, while the remaining 75% is released at pH 6.75 in the distal small intestine [A19567]. As a result, dexlansoprazole has a peak concentration within 1-2 hours after dosing and another within 4-5 hours [FDA Label]. Dexlansoprazole's unique pharmacokinetics addresses limitations of the older generation PPIs including short plasma half-life, break-through symptoms, and need for meal-associated dosing [A19568]. These characteristics make dexlansoprazole a good option for people who struggle with adherence and strict dosage timing before meals[A178087, A19566]. Dexlansoprazole exerts its stomach acid-suppressing effects in the same way as other drugs in the PPI family by inhibiting the final step in gastric acid production. Dexlansoprazole targets the (H+, K+)-ATPase enzyme, which is involved in the secretion of hydrochloric acid through the exchange of H+ ions from the cytoplasm for K+ ions. Normally functioning (H+, K+)-ATPase stimulates hydrochloric acid secretion into the gastric lumen thereby increasing stomach acidity and lowering pH. Once absorbed into circulation, dexlansoprazole covalently binds to the sulfhydryl groups of cysteines found on the (H+, K+)-ATPase enzyme at the secretory surface of gastric parietal cells, which leads to inhibition of both basal and stimulated gastric acid secretion. Despite dexlansoprazole's unique pharmacokinetic profile, efficacy in management of GERD symptoms is considered similar to other medications within the PPI class including [DB00338], [DB00736], [DB00448], [DB00213], and [DB01129]. Due to their good safety profile and as several PPIs are available over the counter without a prescription, their current use in North America is widespread. Long term use of PPIs such as dexlansoprazole have been associated with possible adverse effects, however, including increased susceptibility to bacterial infections (including gastrointestinal _C. difficile_), reduced absorption of micronutrients including iron and B12, and an increased risk of developing hypomagnesemia and hypocalcemia which may contribute to osteoporosis and bone fractures later in life [A177571]. PPIs such as dexlansoprazole have also been shown to inhibit the activity of dimethylarginine dimethylaminohydrolase (DDAH), an enzyme necessary for cardiovascular health. DDAH inhibition causes a consequent accumulation of the nitric oxide synthase inhibitor asymmetric dimethylarginine (ADMA), which is thought to cause the association of PPIs with increased risk of cardiovascular events in patients with unstable coronary syndromes [A177577, A177580]. Dexlansoprazole doses should be slowly lowered, or tapered, before discontinuing as rapid discontinuation of PPIs such as dexlansoprazole may cause a rebound effect and a short term increase in hypersecretion [A177574].
DB00736EsomeprazoleEsomeprazole, sold under the brand name Nexium, is a proton pump inhibitor (PPI) medication used for the management of gastroesophageal reflux disease (GERD), for gastric protection to prevent recurrence of stomach ulcers or gastric damage from chronic use of NSAIDs, and for the treatment of pathological hypersecretory conditions including Zollinger-Ellison (ZE) Syndrome. It can also be found in quadruple regimens for the treatment of _H. pylori_ infections along with other antibiotics including [DB01060], [DB01211], and [DB00916], for example.[A177271, F4498] Its efficacy is considered similar to other medications within the PPI class including [DB00338], [DB00213], [DB00448], [DB05351], and [DB01129]. Esomeprazole is the s-isomer of [DB00338], which is a racemate of the S- and R-enantiomer. Esomeprazole has been shown to inhibit acid secretion to a similar extent as [DB00338], without any significant differences between the two compounds _in vitro_. Esomeprazole exerts its stomach acid-suppressing effects by preventing the final step in gastric acid production by covalently binding to sulfhydryl groups of cysteines found on the (H+, K+)-ATPase enzyme at the secretory surface of gastric parietal cells. This effect leads to inhibition of both basal and stimulated gastric acid secretion, irrespective of the stimulus. As the binding of esomeprazole to the (H+, K+)-ATPase enzyme is irreversible and new enzyme needs to be expressed in order to resume acid secretion, esomeprazole's duration of antisecretory effect persists longer than 24 hours.[FDA Label] PPIs such as esomeprazole have also been shown to inhibit the activity of dimethylarginine dimethylaminohydrolase (DDAH), an enzyme necessary for cardiovascular health. DDAH inhibition causes a consequent accumulation of the nitric oxide synthase inhibitor asymmetric dimethylarginie (ADMA), which is thought to cause the association of PPIs with increased risk of cardiovascular events in patients with unstable coronary syndromes.[A177577, A177580] Due to their good safety profile and as several PPIs are available over the counter without a prescription, their current use in North America is widespread. Long term use of PPIs such as esomeprazole has been associated with possible adverse effects, however, including increased susceptibility to bacterial infections (including gastrointestinal _C. difficile_), reduced absorption of micronutrients such as iron and B12, and an increased risk of developing hypomagnesemia and hypocalcemia which may contribute to osteoporosis and bone fractures later in life.[A177571] Rapid discontinuation of PPIs such as esomeprazole may cause a rebound effect and a short term increase in hypersecretion.[A177574] Esomeprazole doses should be slowly lowered, or tapered, before discontinuing to prevent this rebound effect.
DB00338OmeprazoleOriginally approved by the FDA in 1989, omeprazole is a _proton-pump inhibitor_, used to treat gastric acid-related disorders. These disorders may include gastroesophageal reflux disease (GERD), peptic ulcer disease, and other diseases characterized by the oversecretion of gastric acid. This drug was the first clinical useful drug in its class, and its approval was followed by the formulation of many other proton pump inhibitor drugs [A174232]. Omeprazole is generally effective and well-tolerated, promoting its popular use in children and adults [FDA label].
DB00213PantoprazolePantoprazole is a first-generation proton pump inhibitor (PPI) used for the management of gastroesophageal reflux disease (GERD), for gastric protection to prevent recurrence of stomach ulcers or gastric damage from chronic use of NSAIDs, and for the treatment of pathological hypersecretory conditions including Zollinger-Ellison (ZE) Syndrome. It can also be found in quadruple regimens for the treatment of _H. pylori_ infections along with other antibiotics including [DB01060], [DB01211], and [DB00916], for example.[A177271][F4498] Its efficacy is considered similar to other medications within the PPI class including [DB00338], [DB00736], [DB00448], [DB05351], and [DB01129]. Pantoprazole exerts its stomach acid-suppressing effects by preventing the final step in gastric acid production by covalently binding to sulfhydryl groups of cysteines found on the (H+, K+)-ATPase enzyme at the secretory surface of gastric parietal cell. This effect leads to inhibition of both basal and stimulated gastric acid secretion, irrespective of the stimulus. As the binding of pantoprazole to the (H+, K+)-ATPase enzyme is irreversible and new enzyme needs to be expressed in order to resume acid secretion, pantoprazole's duration of antisecretory effect persists longer than 24 hours.[FDA Label] Due to their good safety profile and as several PPIs are available over the counter without a prescription, their current use in North America is widespread. Long term use of PPIs such as pantoprazole have been associated with possible adverse effects, however, including increased susceptibility to bacterial infections (including gastrointestinal _C. difficile_), reduced absorption of micronutrients including iron and B12, and an increased risk of developing hypomagnesemia and hypocalcemia which may contribute to osteoporosis and bone fractures later in life.[A177571] PPIs such as pantoprazole have also been shown to inhibit the activity of dimethylarginine dimethylaminohydrolase (DDAH), an enzyme necessary for cardiovascular health. DDAH inhibition causes a consequent accumulation of the nitric oxide synthase inhibitor asymmetric dimethylarginie (ADMA), which is thought to cause the association of PPIs with increased risk of cardiovascular events in patients with unstable coronary syndromes.[A177577, A177580] Pantoprazole doses should be slowly lowered, or tapered, before discontinuing as rapid discontinuation of PPIs such as pantoprazole may cause a rebound effect and a short term increase in hypersecretion.[A177574]
DB00863RanitidineRanitidine is a commonly used drug, classified as a _histamine H2-receptor antagonist_. This drug helps to prevent and treat gastric-acid related conditions, including ulcers, because of its ability to decrease gastric acid secretion [A176759], [FDA label]. It is often referred to as _Zantac_, and is available in various forms, including a regular tablet, injection, and effervescent tablet [FDA label], [F4253]. One common use of this drug is to relieve the symptoms of gastric esophageal reflux disease (GERD) [FDA label], which often leads to heartburn symptoms and acid regurgitation. The prevalence of GERD is thought to be 10-20% in western countries [A176843]. Ranitidine has proven to be an effective agent in relieving the above symptoms and is therefore widely used in GERD and other gastric-acid related conditions [A176849], [FDA label].
DrugDrug NameTargetType
DB05351DexlansoprazolePotassium-transporting ATPase alpha chain 1target
DB05351DexlansoprazoleCytochrome P450 2C19enzyme
DB05351DexlansoprazoleCytochrome P450 3A4enzyme
DB05351DexlansoprazolePotassium-transporting ATPase subunit betatarget
DB05351DexlansoprazoleN(G),N(G)-dimethylarginine dimethylaminohydrolase 1target
DB00736EsomeprazolePotassium-transporting ATPase alpha chain 1target
DB00736EsomeprazoleCytochrome P450 2C19enzyme
DB00736EsomeprazoleCytochrome P450 3A4enzyme
DB00736EsomeprazoleN(G),N(G)-dimethylarginine dimethylaminohydrolase 1target
DB00736EsomeprazoleMultidrug resistance protein 1transporter
DB00736EsomeprazoleSolute carrier family 22 member 8transporter
DB00338OmeprazolePotassium-transporting ATPase alpha chain 1target
DB00338OmeprazoleCytochrome P450 2C19enzyme
DB00338OmeprazoleCytochrome P450 3A4enzyme
DB00338OmeprazoleCytochrome P450 2C9enzyme
DB00338OmeprazoleCytochrome P450 1A2enzyme
DB00338OmeprazoleCanalicular multispecific organic anion transporter 2transporter
DB00338OmeprazoleMultidrug resistance protein 1transporter
DB00338OmeprazoleATP-binding cassette sub-family G member 2transporter
DB00338OmeprazoleCytochrome P450 1A1enzyme
DB00338OmeprazoleCytochrome P450 1B1enzyme
DB00338OmeprazoleCytochrome P450 2C18enzyme
DB00338OmeprazoleCytochrome P450 2C8enzyme
DB00338OmeprazoleCytochrome P450 2D6enzyme
DB00338OmeprazoleAryl hydrocarbon receptortarget
DB00213PantoprazolePotassium-transporting ATPase alpha chain 1target
DB00213PantoprazoleCytochrome P450 2C19enzyme
DB00213PantoprazoleCytochrome P450 3A4enzyme
DB00213PantoprazoleMultidrug resistance protein 1transporter
DB00213PantoprazoleATP-binding cassette sub-family G member 2transporter
DB00213PantoprazoleSolute carrier family 22 member 8transporter
DB00213PantoprazoleN(G),N(G)-dimethylarginine dimethylaminohydrolase 1target
DB00863RanitidineHistamine H2 receptortarget
DB00863RanitidineCytochrome P450 1A2enzyme
DB00863RanitidineCytochrome P450 2D6enzyme
DB00863RanitidineSolute carrier family 22 member 1transporter
DB00863RanitidineMultidrug resistance protein 1transporter
DB00863RanitidineSolute carrier family 22 member 8transporter
DB00863RanitidineCytochrome P450 3A4enzyme
DB00863RanitidineAcetylcholinesterasetarget
DB00863RanitidineSolute carrier family 22 member 2transporter
DB00863RanitidineCholinesterasetarget
DrugDrug NamePhaseStatusCount
DB05351Dexlansoprazole1Completed1
DB05351Dexlansoprazole2Completed1
DB05351Dexlansoprazole2Not Yet Recruiting1
DB00736Esomeprazole2Completed1
DB05351Dexlansoprazole3Terminated1
DB00736Esomeprazole3Completed2
DB00736Esomeprazole3Not Yet Recruiting2
DB00927Famotidine3Completed1
DB11964Ilaprazole3Completed1
DB12770Lafutidine3Completed1
DB00448Lansoprazole3Completed5
DB00448Lansoprazole3Terminated1
DB00338Omeprazole3Completed1
DB11739Vonoprazan3Completed2
DB00736Esomeprazole4Completed5
DB00448Lansoprazole4Active Not Recruiting1
DB00448Lansoprazole4Completed2
DB00338Omeprazole4Completed1
DB01390Sodium bicarbonate4Completed1
DB11739Vonoprazan4Active Not Recruiting1