Identification

Name
Dexlansoprazole
Accession Number
DB05351
Type
Small Molecule
Groups
Approved, Investigational
Description

Dexlansoprazole is an oral delayed-release drug for the treatment of erosive esophagitis and gastro-oesophageal reflux disease for adult patients as well as patients aged 12-17. Approved in 2009 by FDA, it is available as a delayed-release capsule and delayed-release orally disintegrating tablets (SoluTab). Dexlansoprazole is a proton pump inhibitor and R-enantiomer of lansoprazole. Its dual-delivery system is intended for extended plasma concentration and therapeutic effects, in comparison to other single-release proton pump inhibitors. Capsule formulation of dexlansoprazole also allows dosing at any time of the day without regard to meals [1].

Structure
Thumb
Synonyms
  • 2-((R)-((3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridinyl)methyl)sulfinyl)-1H-benzimidazole
External IDs
T-168390 / TAK-390 / TAK-390MR
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
DexilantCapsule, delayed release60 mg/1OralPhysicians Total Care, Inc.2010-08-19Not applicableUs64764 0175 30 nlmimage10 4939a49d
DexilantCapsule, delayed release30 mgNasogastric; OralTakeda2010-08-05Not applicableCanada
DexilantCapsule, delayed release60 mg/1OralCardinal Health2010-04-12Not applicableUs55154 515420180913 8702 1mm32n9
DexilantCapsule, delayed release60 mg/1OralTakeda2010-04-12Not applicableUs
DexilantCapsule, delayed release60 mgNasogastric; OralTakeda2010-08-05Not applicableCanada
DexilantCapsule, delayed release30 mg/1OralTakeda2010-04-12Not applicableUs64764 0171 30 nlmimage10 4d39a6ad
Dexilant SoluTabTablet, orally disintegrating, delayed release30 mg/1OralTakeda Pharmaceuticals America, Inc.2016-01-262016-08-03Us
KapidexCapsule, delayed release60 mg/1OralTakeda2009-01-302013-05-31Us
KapidexCapsule, delayed release30 mg/1OralPhysicians Total Care, Inc.2009-03-05Not applicableUs
KapidexCapsule, delayed release60 mg/1OralTakeda Pharmaceutical Company Limited2009-02-132013-05-31Us
Categories
UNII
UYE4T5I70X
CAS number
138530-94-6
Weight
Average: 369.36
Monoisotopic: 369.075882366
Chemical Formula
C16H14F3N3O2S
InChI Key
MJIHNNLFOKEZEW-RUZDIDTESA-N
InChI
InChI=1S/C16H14F3N3O2S/c1-10-13(20-7-6-14(10)24-9-16(17,18)19)8-25(23)15-21-11-4-2-3-5-12(11)22-15/h2-7H,8-9H2,1H3,(H,21,22)/t25-/m1/s1
IUPAC Name
2-[(R)-[3-methyl-4-(2,2,2-trifluoroethoxy)pyridin-2-yl]methanesulfinyl]-1H-1,3-benzodiazole
SMILES
CC1=C(OCC(F)(F)F)C=CN=C1C[S@@](=O)C1=NC2=CC=CC=C2N1

Pharmacology

Indication

Indicated for healing all grades of erosive esophagitis (EE), maintaining and healing of EE and relief of heartburn, and treating heartburn associated with symptomatic non-erosive gastroesophageal reflux disease (GERD).

Associated Conditions
Pharmacodynamics

Dexlansoprazole is a proton pump inhibitor (PPI) and is included in the drug class of antisecretory compounds, the substituted benzimidazoles. It blocks the final step of gastric acid secretion by specific inhibition of the (H+, K+)-ATPase at the secretory surface of the parietal cells on gastric mucosa. The delivery technology of dexlansoprazole MR is designed to release the drug in two separate pH-dependent phases, the first in the proximal duodenum (25% of total drug dose) and the second (75% of total drug dose) in the more distal small intestine. Dexlansoprazole reduces both basal and stimulated gastric acid secretion.

Mechanism of action

H/K ATPase is involved in the secretion of hydrochloric acid, hydrolyzing ATP and exchanging H+ ions from the cytoplasm for K+ ions in the secretory canaliculus, which results in HCl secretion into the gastric lumen. Dexlansoprazole inhibits this effect of H/K ATPase by demonstrating a high degree of activation in the acidic environment. After passing through the liver and reaching the gastric parietal cells activated by a meal, PPIs undergo protonation in the acidic pH environment, followed by conversion to sulphenamide which represents the active form of the drug. Sulphenamide inhibits the activity of the proton pump and hence the transport of hydrogen ions into the gastric lumen via covalent binding to the SH groups of the cysteine residues of H/K ATPase [2].

TargetActionsOrganism
APotassium-transporting ATPase alpha chain 1
inhibitor
Human
APotassium-transporting ATPase subunit beta
inhibitor
Human
Absorption

After oral administration, the peak plasma concentration increases approximately dose proportionally. The dual delayed release formulation achieves two plasma concentration peaks, where the first peak occurs one to two hours after administration, followed by a second peak within four to five hours. The median time (Tmax) to peak plasma concentrations (Cmax) of 30 mg dexlansoprazole SoluTab tablet was 4 hours and ranged from 1 to 6 hours with the Cmax value of 688 ng/mL.

Volume of distribution

The apparent volume of distribution after multiple doses in symptomatic GERD patients was 40 L.

Protein binding

Plasma protein binding of dexlansoprazole ranged from 96% to 99% in healthy subjects and was independent of concentration from 0.01 to 20 mcg/mL.

Metabolism

Dexlansoprazole is extensively metabolized in the liver by oxidation, reduction, and subsequent formation of sulfate, glucuronide and glutathione conjugates to inactive metabolites. Oxidative metabolites are formed by the cytochrome P450 (CYP) enzyme system including hydroxylation mainly by CYP2C19, and oxidation to the sulfone by CYP3A4. Dexlansoprazole is the major circulating component in plasma regardless of CYP2C19 metabolizer status. In CYP2C19 intermediate and extensive metabolizers, the major plasma metabolites are 5-hydroxy dexlansoprazole and its glucuronide conjugate, while in CYP2C19 poor metabolizers dexlansoprazole sulfone is the major plasma metabolite.

Route of elimination

Dexlansoprazole is cleared from the body by either fecal excretion (50.7%) or renal excretion (47.6%) following oral ingestion, with no unchanged drug detected in the urine.

Half life

Dexlansoprazole is eliminated with a half-life of approximately one to two hours in healthy subjects and in patients with symptomatic GERD.

Clearance

Apparent clearance (CL/F) in healthy subjects was 11.4 to 11.6 L/hour, respectively, after five days of 30 or 60 mg once daily administration.

Toxicity

Oral LD50 value in mice, rats and dogs is > 5,000 mg/kg. Most commonly reported adverse reactions are diarrhea, abdominal pain, nausea, upper respiratory tract infection, vomiting, and flatulence. There are no reports of significant overdose but serious adverse events of hypertension have been reported in association with twice daily doses of DEXILANT 60 mg. Nonclicnial toxicology of dexlansopraole was assessed using lansoprazole studies. In two 24-month carcinogenicity studies involving rats, lansoprazole induced dose-related gastric ECL cell hyperplasia and ECL cell carcinoids and increased the incidence of intestinal metaplasia of the gastric epithelium in both sexes of rats. Dexlansoprazole is expected to have no effect on fertility and the reproductive system.

Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Interacting Gene/EnzymeAllele nameGenotype(s)Defining Change(s)Type(s)DescriptionDetails
Cytochrome P450 2C19CYP2C19*2ANot Available681G>AEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2C19CYP2C19*2BNot Available681G>AEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2C19CYP2C19*3Not Available636G>AEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2C19CYP2C19*4Not Available1A>GEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2C19CYP2C19*5Not Available1297C>TEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2C19CYP2C19*6Not Available395G>AEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2C19CYP2C19*7Not Available19294T>AEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2C19CYP2C19*22Not Available557G>C / 991A>GEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2C19CYP2C19*24Not Available99C>T / 991A>G  … show all Effect InferredPoor drug metabolizer.Details
Cytochrome P450 2C19CYP2C19*35Not Available12662A>GEffect InferredPoor drug metabolizer.Details

Interactions

Drug Interactions
DrugInteraction
AbirateroneThe metabolism of Dexlansoprazole can be decreased when combined with Abiraterone.
Acetyl sulfisoxazoleThe metabolism of Dexlansoprazole can be decreased when combined with Acetyl sulfisoxazole.
AlbendazoleThe metabolism of Dexlansoprazole can be decreased when combined with Albendazole.
AlclometasoneThe metabolism of Alclometasone can be decreased when combined with Dexlansoprazole.
Alendronic acidThe therapeutic efficacy of Alendronic acid can be decreased when used in combination with Dexlansoprazole.
AlfuzosinThe metabolism of Dexlansoprazole can be decreased when combined with Alfuzosin.
AlprazolamThe metabolism of Alprazolam can be decreased when combined with Dexlansoprazole.
AmcinonideThe metabolism of Amcinonide can be decreased when combined with Dexlansoprazole.
AmiodaroneThe metabolism of Dexlansoprazole can be decreased when combined with Amiodarone.
AmitriptylineThe metabolism of Amitriptyline can be decreased when combined with Dexlansoprazole.
Food Interactions
Not Available

References

General References
  1. Behm BW, Peura DA: Dexlansoprazole MR for the management of gastroesophageal reflux disease. Expert Rev Gastroenterol Hepatol. 2011 Aug;5(4):439-45. doi: 10.1586/egh.11.37. [PubMed:21780890]
  2. Skrzydlo-Radomanska B, Radwan P: Dexlansoprazole - a new-generation proton pump inhibitor. Prz Gastroenterol. 2015;10(4):191-6. doi: 10.5114/pg.2015.56109. Epub 2015 Dec 16. [PubMed:26759624]
  3. Frye JW, Peura DA: Managing gastroesophageal reflux disease - comparative efficacy and outcomes of dexlansoprazole MR. Ther Clin Risk Manag. 2015 Oct 30;11:1649-56. doi: 10.2147/TCRM.S66680. eCollection 2015. [PubMed:26586949]
  4. Peura DA, Metz DC, Dabholkar AH, Paris MM, Yu P, Atkinson SN: Safety profile of dexlansoprazole MR, a proton pump inhibitor with a novel dual delayed release formulation: global clinical trial experience. Aliment Pharmacol Ther. 2009 Nov 15;30(10):1010-21. doi: 10.1111/j.1365-2036.2009.04137.x. Epub 2009 Sep 4. [PubMed:19735233]
  5. Kukulka M, Wu J, Perez MC: Pharmacokinetics and safety of dexlansoprazole MR in adolescents with symptomatic GERD. J Pediatr Gastroenterol Nutr. 2012 Jan;54(1):41-7. doi: 10.1097/MPG.0b013e31822a323a. [PubMed:21716130]
  6. Fass R, Frazier R: The role of dexlansoprazole modified-release in the management of gastroesophageal reflux disease. Therap Adv Gastroenterol. 2017 Feb;10(2):243-251. doi: 10.1177/1756283X16681701. Epub 2017 Jan 5. [PubMed:28203282]
  7. Wittbrodt ET, Baum C, Peura DA: Delayed release dexlansoprazole in the treatment of GERD and erosive esophagitis. Clin Exp Gastroenterol. 2009;2:117-28. Epub 2009 Nov 17. [PubMed:21694835]
  8. Grabowski B, Lee RD: Absorption, distribution, metabolism and excretion of [14C]dexlansoprazole in healthy male subjects. Clin Drug Investig. 2012 May 1;32(5):319-32. doi: 10.2165/11630930-000000000-00000. [PubMed:22455762]
External Links
PubChem Compound
9578005
PubChem Substance
347827723
ChemSpider
7852369
ChEBI
135931
ChEMBL
CHEMBL1201863
PharmGKB
PA166110257
Wikipedia
Dexlansoprazole
ATC Codes
A02BC06 — Dexlansoprazole
AHFS Codes
  • 56:28.36 — Proton-pump Inhibitors
FDA label
Download (284 KB)
MSDS
Download (201 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0Enrolling by InvitationOtherGastro Esophageal Reflux1
1CompletedNot AvailableBone and Bones / Homeostasis1
1CompletedNot AvailableHealthy Volunteers2
1CompletedNot AvailableReflux, Gastroesophageal1
1CompletedBasic ScienceGastroesophageal Reflux Disease / Heartburn1
1CompletedTreatmentBioavailability1
1CompletedTreatmentErosive Esophagitis(EE) / Gastroesophageal Reflux Disease / Heartburn1
1CompletedTreatmentHealthy Volunteers2
1CompletedTreatmentReflux, Gastroesophageal1
1CompletedTreatmentSafety Issues1
1SuspendedTreatmentPediatric Gastroesophageal Reflux Disease1
1, 2WithdrawnTreatmentGastroesophageal Reflux Disease / Oesophagitis, Eosinophilic / Swallowing Disorders1
2CompletedTreatmentErosive Esophagitis(EE) / Gastroesophageal Reflux Disease1
2CompletedTreatmentGastroesophageal Reflux Disease1
2RecruitingTreatmentDifferentiated Thyroid Cancer (DTC) / Follicular Thyroid Cancer / Poorly Differentiated Thyroid Gland Carcinoma / Thyroid Cancer, Medullary / Thyroid Cancers / Thyroid Papillary Carcinoma1
2SuspendedTreatmentErosive Esophagitis(EE)1
2SuspendedTreatmentReflux, Gastroesophageal1
2, 3RecruitingTreatmentNon Cardiac Chest Pain1
3CompletedTreatmentGastroesophageal Reflux Disease4
3CompletedTreatmentGastroesophageal Reflux Disease / Heartburn1
3CompletedTreatmentPeptic Esophagitis / Reflux Esophagitis (RE)5
3CompletedTreatmentReflux, Gastroesophageal2
3TerminatedTreatmentErosive Esophagitis(EE)1
4CompletedTreatmentEsophagus, Barrett / Inflammatory Reaction1
4CompletedTreatmentGastro-esophageal Reflux Disease (GERD) / Proton Pump Inhibitor1
4CompletedTreatmentGastroesophageal Reflux Disease1
4Enrolling by InvitationTreatmentGastroesophageal Reflux Disease1
4RecruitingTreatmentH Pylori Infection Eradication1
4TerminatedTreatmentEsophagus, Barrett1
4Unknown StatusTreatmentHypertrophy of Lingual Tonsil / Laryngopharyngeal Reflux1
4WithdrawnTreatmentGastrointestinal Reflux Disease / Thoracic Pain1
Not AvailableCompletedNot AvailableHelicobacter Infections1
Not AvailableCompletedTreatmentSuspected Eosinophilic Esophagitis1
Not AvailableRecruitingTreatmentCompare the Response Rate of Atypical GERD After PPI Therapy1
Not AvailableTerminatedTreatmentLaryngopharyngeal Reflux1
Not AvailableUnknown StatusTreatmentLaryngopharyngeal Reflux1
Not AvailableWithdrawnTreatmentGastroesophageal Reflux Disease / Head and Neck Carcinoma / Oropharyngeal Cancers1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
Capsule, delayed releaseNasogastric; Oral30 mg
Capsule, delayed releaseNasogastric; Oral60 mg
Capsule, delayed releaseOral60 mg/1
Tablet, orally disintegrating, delayed releaseOral30 mg/1
Capsule, delayed releaseOral30 mg/1
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
CA1327010No1994-02-152011-02-15Canada
CA2375201No2010-02-092020-06-15Canada
US7399485Yes1998-11-262018-11-26Us
US6328994Yes1999-11-172019-11-17Us
US7875292Yes1999-11-172019-11-17Us
US7431942Yes1999-11-172019-11-17Us
US6462058Yes2000-12-152020-12-15Us
US6939971Yes2000-12-152020-12-15Us
US8173158Yes2010-09-172030-09-17Us
US6664276Yes2003-07-302023-07-30Us
US8784885Yes2004-04-152024-04-15Us
US9233103No2012-03-052032-03-05Us
US9011926No2006-02-242026-02-24Us
US9238029No2006-01-172026-01-17Us
US8722084Yes2004-04-152024-04-15Us
US9145389No2000-06-152020-06-15Us
US8871273Yes2008-07-112028-07-11Us
US8461187Yes2006-07-172026-07-17Us
US8105626Yes2007-03-272027-03-27Us
US7285668Yes2000-12-152020-12-15Us
US7790755Yes2007-02-022027-02-02Us
US9241910No2009-03-102029-03-10Us
US6238994Yes1999-11-172019-11-17Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)Decomposes at 140ºCMSDS
water solubility0.21mg/mL at pH7.0MSDS
logP2.38MSDS
pKa8.87MSDS
Predicted Properties
PropertyValueSource
Water Solubility0.25 mg/mLALOGPS
logP2.84ALOGPS
logP3.03ChemAxon
logS-3.2ALOGPS
pKa (Strongest Acidic)9.35ChemAxon
pKa (Strongest Basic)4.16ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area67.87 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity87.61 m3·mol-1ChemAxon
Polarizability34.5 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as sulfinylbenzimidazoles. These are polycyclic aromatic compounds containing a sulfinyl group attached at the position 2 of a benzimidazole moiety.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Benzimidazoles
Sub Class
Sulfinylbenzimidazoles
Direct Parent
Sulfinylbenzimidazoles
Alternative Parents
Methylpyridines / Alkyl aryl ethers / Benzenoids / Imidazoles / Heteroaromatic compounds / Sulfoxides / Sulfinyl compounds / Azacyclic compounds / Organopnictogen compounds / Organonitrogen compounds
show 4 more
Substituents
Sulfinylbenzimidazole / Alkyl aryl ether / Methylpyridine / Pyridine / Benzenoid / Azole / Imidazole / Heteroaromatic compound / Sulfoxide / Azacycle
show 15 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Sodium:potassium-exchanging atpase activity
Specific Function
Catalyzes the hydrolysis of ATP coupled with the exchange of H(+) and K(+) ions across the plasma membrane. Responsible for acid production in the stomach.
Gene Name
ATP4A
Uniprot ID
P20648
Uniprot Name
Potassium-transporting ATPase alpha chain 1
Molecular Weight
114117.74 Da
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Hydrogen:potassium-exchanging atpase activity
Specific Function
Required for stabilization and maturation of the catalytic proton pump alpha subunit and may also involved in cell adhesion and establishing epithelial cell polarity.
Gene Name
ATP4B
Uniprot ID
P51164
Uniprot Name
Potassium-transporting ATPase subunit beta
Molecular Weight
33366.95 Da

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
Gene Name
CYP2C19
Uniprot ID
P33261
Uniprot Name
Cytochrome P450 2C19
Molecular Weight
55930.545 Da
References
  1. Goh KL, Choi MG, Hsu PI, Chun HJ, Mahachai V, Kachintorn U, Leelakusolvong S, Kim N, Rani AA, Wong BC, Wu J, Chiu CT, Shetty V, Bocobo JC, Chan MM, Lin JT: Pharmacological and Safety Profile of Dexlansoprazole: A New Proton Pump Inhibitor - Implications for Treatment of Gastroesophageal Reflux Disease in the Asia Pacific Region. J Neurogastroenterol Motil. 2016 Jul 30;22(3):355-66. doi: 10.5056/jnm15150. [PubMed:26932927]
  2. Dexlanzoprazole FDA label [File]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da

Drug created on November 18, 2007 11:24 / Updated on September 22, 2018 22:34