Dapagliflozin

Identification

Summary

Dapagliflozin is a sodium-glucose cotransporter 2 inhibitor used in the management of type 2 diabetes mellitus.

Brand Names
Edistride, Farxiga, Forxiga, Qtern, Qternmet, Xigduo
Generic Name
Dapagliflozin
DrugBank Accession Number
DB06292
Background

Dapagliflozin is a sodium-glucose cotransporter 2 (SGLT2) inhibitor, and it was the first SLGT2 inhibitor to be approved. indicated for managing diabetes mellitus type 2.3 When combined with diet and exercise in adults, dapagliflozin helps to improve glycemic control by inhibiting glucose reabsorption in the proximal tubule of the nephron and causing glycosuria.1 Dapagliflozin has been investigated either as monotherapy or as an adjunct treatment with insulin or other oral hypoglycemic agents.4

Dapagliflozin was originally approved by the FDA on Jan 08, 2014, to improve glycemic control in adults with type 2 diabetes in conjunction with diet and exercise.12 It was later approved to reduce the risk of kidney function decline, kidney failure, cardiovascular death, and hospitalization for heart failure in adults with chronic kidney disease in April 2021.12

Type
Small Molecule
Groups
Approved
Structure
Weight
Average: 408.873
Monoisotopic: 408.133966239
Chemical Formula
C21H25ClO6
Synonyms
  • (2S,3R,4R,5S,6R)-2-(4-Chloro-3-(4-ethoxybenzyl)phenyl)-6- (hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol
  • Dapagliflozin
  • Dapagliflozina
External IDs
  • BMS 512148
  • BMS-512148

Pharmacology

Indication

Dapagliflozin is indicated as an adjunct treatment to improve glycemic control in adult patients with type 2 diabetes mellitus along with diet and exercise.9,1,2For patients with chronic kidney disease at risk of progression, dapagliflozin in used to reduce the risk of sustained eGFR decline, end-stage kidney disease, cardiovascular death, and hospitalization for heart failure.9 Dapagliflozin is also indicated to either reduce the risk of cardiovascular death, hospitalization for heart failure, and urgent heart failure visit in adults with heart failure or reduce the risk of hospitalization for heart failure in adults with type 2 diabetes mellitus and either established cardiovascular disease or multiple cardiovascular risk factors.9 Combination products with dapagliflozin also exist, either as a dapagliflozin-saxagliptin or dapagliflozin-metformin hydrochloride formulation.7,8 Both are used as an adjunct treatment to diet and exercise to improve glycemic control in adults with type 2 diabetes.7,8

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Prevention ofCardiovascular mortality•••••••••••••••••••••••
Prevention ofCardiovascular mortality••••••••••••••••••••• •••• ••• ••••••••••• •• •••••• •••••••••••••
Prevention ofEnd stage renal disease (esrd)••••••••••••••••••••• •••• ••• ••••••••••• •• •••••• •••••••••••••
Prevention ofHospitalizations•••••••••••••••••••••••••••••••• •••• •••••••• •••• • •••••••• ••••••••••••••
Prevention ofHospitalizations••••••••••••••••••••• • •••••••• ••••••••• ••••••••••• •••••••••••••• •••••••••••••
Contraindications & Blackbox Warnings
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Pharmacodynamics

Dapagliflozin also reduces sodium reabsorption and increases the delivery of sodium to the distal tubule. This may influence several physiological functions including, but not restricted to, lowering both pre- and afterload of the heart and downregulation of sympathetic activity, and decreased intraglomerular pressure which is believed to be mediated by increased tubuloglomerular feedback.10

Increases in the amount of glucose excreted in the urine were observed in healthy subjects and in patients with type 2 diabetes mellitus following the administration of dapagliflozin. Dapagliflozin doses of 5 or 10 mg per day in patients with type 2 diabetes mellitus for 12 weeks resulted in excretion of approximately 70 grams of glucose in the urine per day at Week 12. A near-maximum glucose excretion was observed at the dapagliflozin daily dose of 20 mg. This urinary glucose excretion with dapagliflozin also results in increases in urinary volume. After discontinuation of dapagliflozin, on average, the elevation in urinary glucose excretion approaches baseline by about 3 days for the 10 mg dose.10

Dapagliflozin was not associated with clinically meaningful prolongation of QTc interval at daily doses up to 150 mg (15 times the recommended maximum dose) in a study of healthy subjects. In addition, no clinically meaningful effect on QTc interval was observed following single doses of up to 500 mg (50 times the recommended maximum dose) of dapagliflozin in healthy subjects.10

Mechanism of action

Dapagliflozin inhibits the sodium-glucose cotransporter 2(SGLT2) which is primarily located in the proximal tubule of the nephron.1 SGLT2 facilitates 90% of glucose reabsorption in the kidneys and so its inhibition allows for glucose to be excreted in the urine.1 This excretion allows for better glycemic control and potentially weight loss in patients with type 2 diabetes mellitus.1

TargetActionsOrganism
ASodium/glucose cotransporter 2
antagonist
inhibitor
Humans
Absorption

Oral dapagliflozin reaches a maximum concentration within 1 hour of administration when patients have been fasting.1 Following oral administration of dapagliflozin, the maximum plasma concentration (Cmax) is usually attained within 2 hours under fasting state. The Cmax and AUC values increase dose proportionally with an increase in dapagliflozin dose in the therapeutic dose range. The absolute oral bioavailability of dapagliflozin following the administration of a 10 mg dose is 78%. Administration of dapagliflozin with a high-fat meal decreases its Cmax by up to 50% and prolongs Tmax by approximately 1 hour but does not alter AUC as compared with the fasted state. These changes are not considered to be clinically meaningful and dapagliflozin can be administered with or without food.10

Volume of distribution

The volume of distribution was estimated to be 118L.2

Protein binding

Dapagliflozin is approximately 91% protein bound. Protein binding is not altered in patients with renal or hepatic impairment.10

Metabolism

Dapagliflozin is primarily glucuronidated to become the inactive 3-O-glucuronide metabolite(60.7%).1,2 Dapagliflozin also produces another minor glucuronidated metabolite(5.4%), a de-ethylated metabolite(<5%), and a hydroxylated metabolite(<5%)1. Metabolism of dapagliflozin is mediated by cytochrome p-450(CYP)1A1, CYP1A2, CYP2A6, CYP2C9, CYP2D6, CYP3A4, uridine diphosphate glucuronyltransferase(UGT)1A9, UGT2B4, and UGT2B72. Glucuronidation to the major metabolite is mediated by UGT1A9.2

Hover over products below to view reaction partners

Route of elimination

Dapagliflozin and related metabolites are primarily eliminated via the renal pathway. Following a single 50 mg dose of [14C]-dapagliflozin, 75% and 21% of total radioactivity is excreted in urine and feces, respectively. In urine, less than 2% of the dose is excreted as the parent drug. In feces, approximately 15% of the dose is excreted as the parent drug.10

Half-life

The mean plasma terminal half-life (t1/2) for dapagliflozin is approximately 12.9 hours following a single oral dose of 10 mg.10 In healthy subjects given a single oral dose of 50 mg of dapagliflozin, the mean terminal half-life was 13.8 hours.1

Clearance

Oral plasma clearance was 4.9 mL/min/kg, and renal clearance was 5.6 mL/min.1

Adverse Effects
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Toxicity

Age, gender, race, and body weight do not affect dapagliflozin dosing requirementsLabel,2. Although age does not affect dosing requirements, safety has not been established in pediatric populations and patients at an especially advanced age may be more susceptible to adverse effectsLabel. Animal studies in pregnancy showed no fetal toxicity in the first trimester but exposure later in pregnancy was associated with renal pelvic dilatation and maternal toxicity at much higher doses than the maximum recommended human doseLabel. Due to this data, dapagliflozin is not recommended in the second and third trimester of pregnancyLabel. Dapagliflozin is excreted in milk from rats, though this may not necessarily be the case in humansLabel. Children under 2 years old who are exposed to dapagliflozin may be at risk of improper kidney developmentLabel. Dapagliflozin is not recommended in patients with a creatinine clearance below 45mL/min and is contraindicated in patients with creatinine clearance below 30mL/minLabel. Dose adjustments are not necessary in patients with hepatic impairment at any stage, although the risk and benefit to the patient must be assessed as there is limited data on dapagliflozin use in this populationLabel.

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbaloparatideThe risk or severity of adverse effects can be increased when Abaloparatide is combined with Dapagliflozin.
AcarboseDapagliflozin may increase the hypoglycemic activities of Acarbose.
AcebutololThe therapeutic efficacy of Dapagliflozin can be increased when used in combination with Acebutolol.
AcetazolamideThe therapeutic efficacy of Dapagliflozin can be increased when used in combination with Acetazolamide.
AcetohexamideDapagliflozin may increase the hypoglycemic activities of Acetohexamide.
Food Interactions
  • Avoid excessive or chronic alcohol consumption. Binge drinking or drinking alcohol often may predispose patients to ketoacidosis.
  • Take with or without food.

Products

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Product Ingredients
IngredientUNIICASInChI Key
Dapagliflozin propanediol monohydrate887K2391VH960404-48-2GOADIQFWSVMMRJ-UPGAGZFNSA-N
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Dapagliflozin ViatrisTablet, film coated10 mgOralViatris Limited2023-04-04Not applicableEU flag
Dapagliflozin ViatrisTablet, film coated5 mgOralViatris Limited2023-04-04Not applicableEU flag
Dapagliflozin ViatrisTablet, film coated5 mgOralViatris Limited2023-04-04Not applicableEU flag
Dapagliflozin ViatrisTablet, film coated5 mgOralViatris Limited2023-04-04Not applicableEU flag
Dapagliflozin ViatrisTablet, film coated10 mgOralViatris Limited2023-04-04Not applicableEU flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Accel-dapagliflozinTablet5 mgOralAccel Pharma IncNot applicableNot applicableCanada flag
Accel-dapagliflozinTablet10 mgOralAccel Pharma IncNot applicableNot applicableCanada flag
Ag-dapagliflozinTablet5 mgOralAngita Pharma Inc.2023-05-15Not applicableCanada flag
Ag-dapagliflozinTablet10 mgOralAngita Pharma Inc.2023-05-15Not applicableCanada flag
Apo-dapagliflozinTablet10 mgOralApotex Corporation2023-05-16Not applicableCanada flag
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
Apo-dapagliflozin-metforminDapagliflozin (5 mg) + Metformin hydrochloride (850 mg)TabletOralApotex Corporation2023-12-14Not applicableCanada flag
Apo-dapagliflozin-metforminDapagliflozin (5 mg) + Metformin hydrochloride (1000 mg)TabletOralApotex Corporation2023-12-01Not applicableCanada flag
Auro-dapagliflozin / MetforminDapagliflozin (5 mg) + Metformin hydrochloride (1000 mg)TabletOralAuro Pharma Inc2023-05-16Not applicableCanada flag
Auro-dapagliflozin / MetforminDapagliflozin (5 mg) + Metformin hydrochloride (850 mg)TabletOralAuro Pharma Inc2023-05-16Not applicableCanada flag
Dapagliflozin and Metformin HydrochlorideDapagliflozin propanediol monohydrate (10 mg/1) + Metformin hydrochloride (1000 mg/1)Tablet, film coated, extended releaseOralPrasco, Llc2024-01-03Not applicableUS flag

Categories

ATC Codes
A10BK01 — DapagliflozinA10BD15 — Metformin and dapagliflozinA10BD21 — Saxagliptin and dapagliflozinA10BD25 — Metformin, saxagliptin and dapagliflozin
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as phenolic glycosides. These are organic compounds containing a phenolic structure attached to a glycosyl moiety. Some examples of phenolic structures include lignans, and flavonoids. Among the sugar units found in natural glycosides are D-glucose, L-Fructose, and L rhamnose.
Kingdom
Organic compounds
Super Class
Organic oxygen compounds
Class
Organooxygen compounds
Sub Class
Carbohydrates and carbohydrate conjugates
Direct Parent
Phenolic glycosides
Alternative Parents
Diphenylmethanes / Hexoses / C-glycosyl compounds / Phenoxy compounds / Phenol ethers / Alkyl aryl ethers / Chlorobenzenes / Aryl chlorides / Oxanes / Secondary alcohols
show 6 more
Substituents
Alcohol / Alkyl aryl ether / Aromatic heteromonocyclic compound / Aryl chloride / Aryl halide / Benzenoid / C-glycosyl compound / Chlorobenzene / Dialkyl ether / Diphenylmethane
show 17 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
aromatic ether, organochlorine compound, C-glycosyl compound (CHEBI:85078)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
1ULL0QJ8UC
CAS number
461432-26-8
InChI Key
JVHXJTBJCFBINQ-ADAARDCZSA-N
InChI
InChI=1S/C21H25ClO6/c1-2-27-15-6-3-12(4-7-15)9-14-10-13(5-8-16(14)22)21-20(26)19(25)18(24)17(11-23)28-21/h3-8,10,17-21,23-26H,2,9,11H2,1H3/t17-,18-,19+,20-,21+/m1/s1
IUPAC Name
(2S,3R,4R,5S,6R)-2-{4-chloro-3-[(4-ethoxyphenyl)methyl]phenyl}-6-(hydroxymethyl)oxane-3,4,5-triol
SMILES
CCOC1=CC=C(CC2=C(Cl)C=CC(=C2)[C@@H]2O[C@H](CO)[C@@H](O)[C@H](O)[C@H]2O)C=C1

References

General References
  1. Obermeier M, Yao M, Khanna A, Koplowitz B, Zhu M, Li W, Komoroski B, Kasichayanula S, Discenza L, Washburn W, Meng W, Ellsworth BA, Whaley JM, Humphreys WG: In vitro characterization and pharmacokinetics of dapagliflozin (BMS-512148), a potent sodium-glucose cotransporter type II inhibitor, in animals and humans. Drug Metab Dispos. 2010 Mar;38(3):405-14. doi: 10.1124/dmd.109.029165. Epub 2009 Dec 8. [Article]
  2. Kasichayanula S, Liu X, Lacreta F, Griffen SC, Boulton DW: Clinical pharmacokinetics and pharmacodynamics of dapagliflozin, a selective inhibitor of sodium-glucose co-transporter type 2. Clin Pharmacokinet. 2014 Jan;53(1):17-27. doi: 10.1007/s40262-013-0104-3. [Article]
  3. Paik J, Blair HA: Correction to: Dapagliflozin: A Review in Type 1 Diabetes. Drugs. 2019 Dec;79(18):2011. doi: 10.1007/s40265-019-01238-2. [Article]
  4. Anderson SL: Dapagliflozin efficacy and safety: a perspective review. Ther Adv Drug Saf. 2014 Dec;5(6):242-54. doi: 10.1177/2042098614551938. [Article]
  5. FDA Drug Approval Package: Dapagliflozin [Link]
  6. FDA Approved Drug Products: Farxiga Dapagliflozin Oral Tablets [Link]
  7. FDA Approved Drug Products: Qtern (dapagliflozin/saxagliptin) tablets for oral use [Link]
  8. FDA Approved Drug Products: Xigduo XR (metformin hydrochloride/dapagliflozin) extended-release tablets for oral use [Link]
  9. FDA Approved Drug Products: FARXIGA® (dapagliflozin) tablets, for oral use (May 2023) [Link]
  10. FDA Approved Drug Products: FARXIGA® (dapagliflozin) tablets, for oral use (September 2023) [Link]
  11. FDA Approved Drug Products: FARXIGA (dapagliflozin) tablets, for oral use [Link]
  12. FDA Approves Treatment for Chronic Kidney Disease [Link]
KEGG Drug
D08897
PubChem Compound
9887712
PubChem Substance
175427068
ChemSpider
8063384
BindingDB
20880
RxNav
1488564
ChEBI
85078
ChEMBL
CHEMBL429910
ZINC
ZINC000003819138
PDBe Ligand
LE6
Drugs.com
Drugs.com Drug Page
Wikipedia
Dapagliflozin
PDB Entries
8hez
FDA label
Download (1.22 MB)
MSDS
Download (62.4 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4Active Not RecruitingPreventionBMD / Lupus Nephritis / SGLT2 Inhibitors1
4Active Not RecruitingPreventionChronic Kidney Disease (CKD) / Metabolic Bone Disorder1
4Active Not RecruitingPreventionLupus Nephritis / SGLT2 Inhibitors / Systemic Lupus Erythematosus1
4Active Not RecruitingTreatmentAortic Stenosis / Transcatether Aortic Valve Implantation1
4Active Not RecruitingTreatmentCoronavirus Disease 2019 (COVID‑19)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
Tablet, film coatedOral10 mg/1
Tablet, film coatedOral5 mg/1
TabletOral10 mg
TabletOral5 mg
Tablet, film coatedOral
Tablet, coatedOral10 mg
Tablet, film coatedOral10 mg
Tablet, film coatedOral5 mg
Tablet, film coatedOral
Tablet, coatedOral
TabletOral
Tablet, film coated, extended releaseOral
Tablet, extended releaseOral
Tablet, film coated, extended releaseOral10 mg
Tablet, film coated, extended releaseOral5 mg
Tablet, extended releaseOral1005.04 mg
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US8216180Yes2012-07-102028-07-12US flag
US8439864Yes2013-05-142028-09-25US flag
US6667061Yes2003-12-232020-11-25US flag
US6495164No2002-12-172020-05-25US flag
US6872700No2005-03-292020-01-14US flag
US6956026No2005-10-182018-01-07US flag
US7741269No2010-06-222018-01-07US flag
US9238076Yes2016-01-192024-10-15US flag
US8906851Yes2014-12-092027-02-18US flag
US7612176Yes2009-11-032025-10-13US flag
US8431685Yes2013-04-302025-10-13US flag
US8461105Yes2013-06-112025-10-13US flag
US8329648Yes2012-12-112027-02-18US flag
US7456254Yes2008-11-252025-12-30US flag
US7563871Yes2009-07-212024-10-15US flag
US6824822Yes2004-11-302023-04-09US flag
US6479065No2002-11-122020-08-10US flag
US7223440Yes2007-05-292022-03-03US flag
USRE44186No2013-04-302023-07-31US flag
US8628799No2014-01-142025-07-13US flag
US8685934No2014-04-012030-05-26US flag
US8501698Yes2013-08-062027-12-20US flag
US6414126No2002-07-022020-10-04US flag
US6515117Yes2003-02-042026-04-04US flag
US6936590No2005-08-302020-10-04US flag
US9198925No2015-12-012020-10-04US flag
US7919598No2011-04-052029-12-16US flag
US8361972Yes2013-01-292028-09-21US flag
US8716251No2014-05-062028-03-21US flag
US7851502No2010-12-142028-08-19US flag
US8221786No2012-07-172028-03-21US flag
US9616028No2017-04-112030-11-12US flag
US9320853Yes2016-04-262028-09-25US flag
US8827963Yes2014-09-092029-08-04US flag
US8712615No2014-04-292030-01-18US flag
US8998876Yes2015-04-072030-07-07US flag
US8758292Yes2014-06-242028-05-12US flag
US8690837Yes2014-04-082029-11-19US flag
US8721615Yes2014-05-132030-07-18US flag
US10973836No2021-04-132040-03-09US flag
US11826376No2019-07-182039-07-18US flag

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)65[MSDS]
boiling point (°C)609[MSDS]
logP2.7[MSDS]
Predicted Properties
PropertyValueSource
Water Solubility0.173 mg/mLALOGPS
logP2.52ALOGPS
logP2.11Chemaxon
logS-3.4ALOGPS
pKa (Strongest Acidic)12.57Chemaxon
pKa (Strongest Basic)-3Chemaxon
Physiological Charge0Chemaxon
Hydrogen Acceptor Count6Chemaxon
Hydrogen Donor Count4Chemaxon
Polar Surface Area99.38 Å2Chemaxon
Rotatable Bond Count6Chemaxon
Refractivity104.93 m3·mol-1Chemaxon
Polarizability42.88 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/MSsplash10-0a4i-0004900000-37d5265038fa7c24626e
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-0a4i-2004900000-6928e6b6d57bec67ba2d
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-0a4v-0189200000-93e1a5b8bad4db74540d
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-001i-9106100000-9a396305692d475c12d7
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-0a4r-4397100000-1b671b635a693b641833
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-06si-5369100000-47981f8cfa2a05bfee8a
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-186.7367
predicted
DeepCCS 1.0 (2019)
[M+H]+189.13226
predicted
DeepCCS 1.0 (2019)
[M+Na]+195.51756
predicted
DeepCCS 1.0 (2019)

Targets

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Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Antagonist
Inhibitor
General Function
Low-affinity glucose:sodium symporter activity
Specific Function
Sodium-dependent glucose transporter. Has a Na(+) to glucose coupling ratio of 1:1.Efficient substrate transport in mammalian kidney is provided by the concerted action of a low affinity high capac...
Gene Name
SLC5A2
Uniprot ID
P31639
Uniprot Name
Sodium/glucose cotransporter 2
Molecular Weight
72895.995 Da
References
  1. Obermeier M, Yao M, Khanna A, Koplowitz B, Zhu M, Li W, Komoroski B, Kasichayanula S, Discenza L, Washburn W, Meng W, Ellsworth BA, Whaley JM, Humphreys WG: In vitro characterization and pharmacokinetics of dapagliflozin (BMS-512148), a potent sodium-glucose cotransporter type II inhibitor, in animals and humans. Drug Metab Dispos. 2010 Mar;38(3):405-14. doi: 10.1124/dmd.109.029165. Epub 2009 Dec 8. [Article]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Retinoic acid binding
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform has specificity for phenols. Isoform 2 lacks trans...
Gene Name
UGT1A9
Uniprot ID
O60656
Uniprot Name
UDP-glucuronosyltransferase 1-9
Molecular Weight
59940.495 Da
References
  1. Kasichayanula S, Liu X, Lacreta F, Griffen SC, Boulton DW: Clinical pharmacokinetics and pharmacodynamics of dapagliflozin, a selective inhibitor of sodium-glucose co-transporter type 2. Clin Pharmacokinet. 2014 Jan;53(1):17-27. doi: 10.1007/s40262-013-0104-3. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Glucuronosyltransferase activity
Specific Function
UDPGTs are of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isozyme is active on polyhydroxylated estrogens (such as...
Gene Name
UGT2B4
Uniprot ID
P06133
Uniprot Name
UDP-glucuronosyltransferase 2B4
Molecular Weight
60512.035 Da
References
  1. Kasichayanula S, Liu X, Lacreta F, Griffen SC, Boulton DW: Clinical pharmacokinetics and pharmacodynamics of dapagliflozin, a selective inhibitor of sodium-glucose co-transporter type 2. Clin Pharmacokinet. 2014 Jan;53(1):17-27. doi: 10.1007/s40262-013-0104-3. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Glucuronosyltransferase activity
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds.Its unique specificity for 3,4-catechol estrogens and estriol su...
Gene Name
UGT2B7
Uniprot ID
P16662
Uniprot Name
UDP-glucuronosyltransferase 2B7
Molecular Weight
60694.12 Da
References
  1. Kasichayanula S, Liu X, Lacreta F, Griffen SC, Boulton DW: Clinical pharmacokinetics and pharmacodynamics of dapagliflozin, a selective inhibitor of sodium-glucose co-transporter type 2. Clin Pharmacokinet. 2014 Jan;53(1):17-27. doi: 10.1007/s40262-013-0104-3. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
Curator comments
Based on in vitro data with recombinant CYP isoforms
General Function
Vitamin d 24-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 oxidizes a variety of structurally un...
Gene Name
CYP1A1
Uniprot ID
P04798
Uniprot Name
Cytochrome P450 1A1
Molecular Weight
58164.815 Da
References
  1. Kasichayanula S, Liu X, Lacreta F, Griffen SC, Boulton DW: Clinical pharmacokinetics and pharmacodynamics of dapagliflozin, a selective inhibitor of sodium-glucose co-transporter type 2. Clin Pharmacokinet. 2014 Jan;53(1):17-27. doi: 10.1007/s40262-013-0104-3. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
Curator comments
Based on in vitro data with recombinant CYP isoforms
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
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 oxidizes a variety of structurally un...
Gene Name
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
Molecular Weight
58293.76 Da
References
  1. Kasichayanula S, Liu X, Lacreta F, Griffen SC, Boulton DW: Clinical pharmacokinetics and pharmacodynamics of dapagliflozin, a selective inhibitor of sodium-glucose co-transporter type 2. Clin Pharmacokinet. 2014 Jan;53(1):17-27. doi: 10.1007/s40262-013-0104-3. [Article]
  2. Forxiga Assessment report [File]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
Curator comments
Based on in vitro data with recombinant CYP isoforms
General Function
Steroid hydroxylase activity
Specific Function
Exhibits a high coumarin 7-hydroxylase activity. Can act in the hydroxylation of the anti-cancer drugs cyclophosphamide and ifosphamide. Competent in the metabolic activation of aflatoxin B1. Const...
Gene Name
CYP2A6
Uniprot ID
P11509
Uniprot Name
Cytochrome P450 2A6
Molecular Weight
56501.005 Da
References
  1. Kasichayanula S, Liu X, Lacreta F, Griffen SC, Boulton DW: Clinical pharmacokinetics and pharmacodynamics of dapagliflozin, a selective inhibitor of sodium-glucose co-transporter type 2. Clin Pharmacokinet. 2014 Jan;53(1):17-27. doi: 10.1007/s40262-013-0104-3. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
Curator comments
Based on in vitro data with recombinant CYP isoforms
General Function
Steroid 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 oxidizes a variety of structurally un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. Kasichayanula S, Liu X, Lacreta F, Griffen SC, Boulton DW: Clinical pharmacokinetics and pharmacodynamics of dapagliflozin, a selective inhibitor of sodium-glucose co-transporter type 2. Clin Pharmacokinet. 2014 Jan;53(1):17-27. doi: 10.1007/s40262-013-0104-3. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
Curator comments
Based on in vitro data with recombinant CYP isoforms
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. Kasichayanula S, Liu X, Lacreta F, Griffen SC, Boulton DW: Clinical pharmacokinetics and pharmacodynamics of dapagliflozin, a selective inhibitor of sodium-glucose co-transporter type 2. Clin Pharmacokinet. 2014 Jan;53(1):17-27. doi: 10.1007/s40262-013-0104-3. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
Curator comments
Based on in vitro data with recombinant CYP isoforms
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
References
  1. Kasichayanula S, Liu X, Lacreta F, Griffen SC, Boulton DW: Clinical pharmacokinetics and pharmacodynamics of dapagliflozin, a selective inhibitor of sodium-glucose co-transporter type 2. Clin Pharmacokinet. 2014 Jan;53(1):17-27. doi: 10.1007/s40262-013-0104-3. [Article]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. Kasichayanula S, Liu X, Lacreta F, Griffen SC, Boulton DW: Clinical pharmacokinetics and pharmacodynamics of dapagliflozin, a selective inhibitor of sodium-glucose co-transporter type 2. Clin Pharmacokinet. 2014 Jan;53(1):17-27. doi: 10.1007/s40262-013-0104-3. [Article]

Drug created at March 19, 2008 16:22 / Updated at March 18, 2024 16:48