Details of the Drug

General Information of Drug (ID: DMRF9YK)

Drug Name
Empagliflozin
Synonyms
864070-44-0; JARDIANCE; BI 10773; UNII-HDC1R2M35U; Empagliflozin (BI 10773); BI-10773; BI10773; HDC1R2M35U; CHEBI:82720; 1-chloro-4-(glucopyranos-1-yl)-2-(4-(tetrahydrofuran-3-yloxy)benzyl)benzene; AK160980; (1S)-1,5-anhydro-1-(4-chloro-3-{4-[(3S)-tetrahydrofuran-3-yloxy]benzyl}phenyl)-D-glucitol; (2S,3R,4R,5S,6R)-2-(4-chloro-3-(4-(((S)-tetrahydrofuran-3-yl)oxy)benzyl)phenyl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol
Indication
Disease Entry ICD 11 Status REF
Type-1 diabetes 5A10 Approved [1], [2]
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 450.9
Topological Polar Surface Area (xlogp) 2
Rotatable Bond Count (rotbonds) 6
Hydrogen Bond Donor Count (hbonddonor) 4
Hydrogen Bond Acceptor Count (hbondacc) 7
ADMET Property
Absorption AUC
The area under the plot of plasma concentration (AUC) of drug is 1.870 micromolh/L [3]
Absorption Cmax
The maximum plasma concentration (Cmax) of drug is 0.259 micromol/L [3]
Absorption Tmax
The time to maximum plasma concentration (Tmax) is 1.5 h [3]
BDDCS Class
Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 1: high solubility and high permeability [4]
Clearance
The apparent oral clearance of drug is 10.6 L/h [3]
Elimination
After oral administration of radiolabeled empagliflozin approximately 41.2% of the administered dose was found eliminated in feces and 54.4% eliminated in urine [3]
Half-life
The concentration or amount of drug in body reduced by one-half in 12.4 hours [3]
Metabolism
The drug is metabolized via the glucuronidation [3]
Vd
The volume of distribution (Vd) of drug is 73.8 L [3]
Chemical Identifiers
Formula
C23H27ClO7
IUPAC Name
(2S,3R,4R,5S,6R)-2-[4-chloro-3-[[4-[(3S)-oxolan-3-yl]oxyphenyl]methyl]phenyl]-6-(hydroxymethyl)oxane-3,4,5-triol
Canonical SMILES
C1COC[C@H]1OC2=CC=C(C=C2)CC3=C(C=CC(=C3)[C@H]4[C@@H]([C@H]([C@@H]([C@H](O4)CO)O)O)O)Cl
InChI
InChI=1S/C23H27ClO7/c24-18-6-3-14(23-22(28)21(27)20(26)19(11-25)31-23)10-15(18)9-13-1-4-16(5-2-13)30-17-7-8-29-12-17/h1-6,10,17,19-23,25-28H,7-9,11-12H2/t17-,19+,20+,21-,22+,23-/m0/s1
InChIKey
OBWASQILIWPZMG-QZMOQZSNSA-N
Cross-matching ID
PubChem CID
11949646
ChEBI ID
CHEBI:82720
CAS Number
864070-44-0
DrugBank ID
DB09038
TTD ID
D06ALD
VARIDT ID
DR00271
INTEDE ID
DR1755
ACDINA ID
D01043

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Sodium/glucose cotransporter 2 (SGLT2) TTLWPVF SC5A2_HUMAN Modulator [2]

Drug Transporter (DTP)
DTP Name DTP ID UniProt ID MOA REF
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [5]
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [6]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
UDP-glucuronosyltransferase 2B7 (UGT2B7) DEB3CV1 UD2B7_HUMAN Substrate [7]
UDP-glucuronosyltransferase 1A9 (UGT1A9) DE85D2P UD19_HUMAN Substrate [7]
UDP-glucuronosyltransferase 1A3 (UGT1A3) DEF2WXN UD13_HUMAN Substrate [7]
UDP-glucuronosyltransferase 1A8 (UGT1A8) DE2GB8N UD18_HUMAN Substrate [7]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Empagliflozin (Comorbidity)
DDI Drug Name DDI Drug ID Severity Mechanism Comorbidity REF
Arn-509 DMT81LZ Moderate Accelerated clearance of Empagliflozin due to the transporter induction by Arn-509. Acute myeloid leukaemia [2A60] [55]
Gilteritinib DMWQ4MZ Moderate Decreased clearance of Empagliflozin due to the transporter inhibition by Gilteritinib. Acute myeloid leukaemia [2A60] [56]
Ag-221 DMS0ZBI Moderate Decreased clearance of Empagliflozin due to the transporter inhibition by Ag-221. BCR-ABL1-negative chronic myeloid leukaemia [2A41] [56]
Erdafitinib DMI782S Moderate Decreased clearance of Empagliflozin due to the transporter inhibition by Erdafitinib. Bladder cancer [2C94] [57]
Tucatinib DMBESUA Moderate Decreased clearance of Empagliflozin due to the transporter inhibition by Tucatinib. Breast cancer [2C60-2C6Y] [58]
PF-04449913 DMSB068 Moderate Decreased clearance of Empagliflozin due to the transporter inhibition by PF-04449913. Chronic myelomonocytic leukaemia [2A40] [55]
Fostemsavir DM50ILT Moderate Decreased clearance of Empagliflozin due to the transporter inhibition by Fostemsavir. Human immunodeficiency virus disease [1C60-1C62] [59]
Bempedoic acid DM1CI9R Moderate Decreased clearance of Empagliflozin due to the transporter inhibition by Bempedoic acid. Hyper-lipoproteinaemia [5C80] [60]
PF-06463922 DMKM7EW Moderate Increased metabolism of Empagliflozin caused by PF-06463922 mediated induction of UGT. Lung cancer [2C25] [56]
Capmatinib DMYCXKL Moderate Decreased clearance of Empagliflozin due to the transporter inhibition by Capmatinib. Lung cancer [2C25] [61]
Lasmiditan DMXLVDT Moderate Decreased clearance of Empagliflozin due to the transporter inhibition by Lasmiditan. Migraine [8A80] [62]
Darolutamide DMV7YFT Moderate Decreased clearance of Empagliflozin due to the transporter inhibition by Darolutamide. Prostate cancer [2C82] [63]
Tedizolid DMG2SKR Moderate Decreased clearance of Empagliflozin due to the transporter inhibition by Tedizolid. Skin and skin-structure infection [1F28-1G0Z] [55]
Fostamatinib DM6AUHV Moderate Decreased clearance of Empagliflozin due to the transporter inhibition by Fostamatinib. Thrombocytopenia [3B64] [64]
⏷ Show the Full List of 14 DDI Information of This Drug

Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG
DIG Name DIG ID PubChem CID Functional Classification
Carmellose sodium E00625 Not Available Disintegrant
Ferric hydroxide oxide yellow E00539 23320441 Colorant
Hydroxypropyl cellulose E00632 Not Available Binding agent; Coating agent; Emulsifying agent; Film/Membrane-forming agent; Modified-release agent; Suspending agent; Viscosity-controlling agent
Hypromellose E00634 Not Available Coating agent
Lactose monohydrate E00393 104938 Binding agent; Diluent; Dry powder inhaler carrier; Lyophilization aid
Magnesium stearate E00208 11177 lubricant
Polyethylene glycol 4000 E00654 Not Available Coating agent; Diluent; Ointment base; Plasticizing agent; Solvent; Suppository base; lubricant
Talc E00520 16211421 Anticaking agent; Diluent; Glidant; lubricant
Titanium dioxide E00322 26042 Coating agent; Colorant; Opacifying agent
Hydrophobic colloidal silica E00285 24261 Anticaking agent; Emulsion stabilizing agent; Glidant; Suspending agent; Viscosity-controlling agent
Cellulose microcrystalline E00698 Not Available Adsorbent; Suspending agent; Diluent
⏷ Show the Full List of 11 Pharmaceutical Excipients of This Drug
Pharmaceutical Formulation
Formulation Name Drug Dosage Dosage Form Route
Empagliflozin 10mg tablet 10mg Tablet Oral
Empagliflozin 25mg tablet 25mg Tablet Oral
Jump to Detail Pharmaceutical Formulation Page of This Drug

References

1 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 4754).
2 2014 FDA drug approvals. Nat Rev Drug Discov. 2015 Feb;14(2):77-81.
3 FDA Approved Drug Products: Jardiance (empagliflozin) oral tablets
4 BDDCS predictions, self-correcting aspects of BDDCS assignments, BDDCS assignment corrections, and classification for more than 175 additional drugs
5 KEGG: new perspectives on genomes, pathways, diseases and drugs. Nucleic Acids Res. 2017 Jan 4;45(D1):D353-D361. (dg:DG01913)
6 KEGG: new perspectives on genomes, pathways, diseases and drugs. Nucleic Acids Res. 2017 Jan 4;45(D1):D353-D361. (dg:DG01665)
7 Empagliflozin (Jardiance): a novel SGLT2 inhibitor for the treatment of type-2 diabetes. P T. 2015 Jun;40(6):364-8.
8 Metabolism and transport of tamoxifen in relation to its effectiveness: new perspectives on an ongoing controversy. Future Oncol. 2014 Jan;10(1):107-22.
9 Determination of UDP-glucuronosyltransferase UGT2B7 activity in human liver microsomes by ultra-performance liquid chromatography with MS detection. J Chromatogr B Analyt Technol Biomed Life Sci. 2008 Jul 1;870(1):84-90.
10 Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.
11 Pharmacokinetic and pharmacodynamic interaction of lorazepam and valproic acid in relation to UGT2B7 genetic polymorphism in healthy subjects. Clin Pharmacol Ther. 2008 Apr;83(4):595-600.
12 PharmGKB summary: mycophenolic acid pathway. Pharmacogenet Genomics. 2014 Jan;24(1):73-9.
13 Pitavastatin: a review in hypercholesterolemia. Am J Cardiovasc Drugs. 2017 Apr;17(2):157-168.
14 Troglitazone glucuronidation in human liver and intestine microsomes: high catalytic activity of UGT1A8 and UGT1A10. Drug Metab Dispos. 2002 Dec;30(12):1462-9.
15 Ezetimibe: a review of its metabolism, pharmacokinetics and drug interactions. Clin Pharmacokinet. 2005;44(5):467-94.
16 Pharmacogenomics of statins: understanding susceptibility to adverse effects. Pharmgenomics Pers Med. 2016 Oct 3;9:97-106.
17 Glucuronidation of nonsteroidal anti-inflammatory drugs: identifying the enzymes responsible in human liver microsomes. Drug Metab Dispos. 2005 Jul;33(7):1027-35.
18 Effect of aging on glucuronidation of valproic acid in human liver microsomes and the role of UDP-glucuronosyltransferase UGT1A4, UGT1A8, and UGT1A10. Drug Metab Dispos. 2009 Jan;37(1):229-36.
19 UGT1A1*28 is associated with decreased systemic exposure of atorvastatin lactone. Mol Diagn Ther. 2013 Aug;17(4):233-7.
20 Cerivastatin, genetic variants, and the risk of rhabdomyolysis. Pharmacogenet Genomics. 2011 May;21(5):280-8.
21 Drug interactions between the immunosuppressant tacrolimus and the cholesterol absorption inhibitor ezetimibe in healthy volunteers. Clin Pharmacol Ther. 2011 Apr;89(4):524-8.
22 Polymorphic expression of UGT1A9 is associated with variable acetaminophen glucuronidation in neonates: a population pharmacokinetic and pharmacogenetic study. Clin Pharmacokinet. 2018 Oct;57(10):1325-1336.
23 Pharmacokinetic interaction involving sorafenib and the calcium-channel blocker felodipine in a patient with hepatocellular carcinoma. Invest New Drugs. 2011 Dec;29(6):1511-4.
24 The evolution of population pharmacokinetic models to describe the enterohepatic recycling of mycophenolic acid in solid organ transplantation and autoimmune disease. Clin Pharmacokinet. 2011 Jan;50(1):1-24.
25 The UDP-glucuronosyltransferase 1A9 enzyme is a peroxisome proliferator-activated receptor alpha and gamma target gene. J Biol Chem. 2003 Apr 18;278(16):13975-83.
26 Uridine 5'-diphospho-glucuronosyltransferase genetic polymorphisms and response to cancer chemotherapy. Future Oncol. 2010 Apr;6(4):563-85.
27 Drug-drug interaction potential of darolutamide: in vitro and clinical studies. Eur J Drug Metab Pharmacokinet. 2019 Dec;44(6):747-759.
28 Differential and special properties of the major human UGT1-encoded gastrointestinal UDP-glucuronosyltransferases enhance potential to control chemical uptake. J Biol Chem. 2004 Jan 9;279(2):1429-41.
29 Glucuronidation of active tamoxifen metabolites by the human UDP glucuronosyltransferases. Drug Metab Dispos. 2007 Nov;35(11):2006-14.
30 Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
31 MDR1 (ABCB1) G1199A (Ser400Asn) polymorphism alters transepithelial permeability and sensitivity to anticancer agents. Cancer Chemother Pharmacol. 2009 Jun;64(1):183-8.
32 Mammalian drug efflux transporters of the ATP binding cassette (ABC) family in multidrug resistance: A review of the past decade. Cancer Lett. 2016 Jan 1;370(1):153-64.
33 Folate transporter expression decreases in the human placenta throughout pregnancy and in pre-eclampsia. Pregnancy Hypertens. 2012 Apr;2(2):123-31.
34 Comparative studies on in vitro methods for evaluating in vivo function of MDR1 P-glycoprotein. Pharm Res. 2001 Dec;18(12):1660-8.
35 Antiestrogens and steroid hormones: substrates of the human P-glycoprotein. Biochem Pharmacol. 1994 Jul 19;48(2):287-92.
36 Association of genetic polymorphisms in the influx transporter SLCO1B3 and the efflux transporter ABCB1 with imatinib pharmacokinetics in patients with chronic myeloid leukemia. Ther Drug Monit. 2011 Apr;33(2):244-50.
37 Doxorubicin transport by RALBP1 and ABCG2 in lung and breast cancer. Int J Oncol. 2007 Mar;30(3):717-25.
38 Wild-type breast cancer resistance protein (BCRP/ABCG2) is a methotrexate polyglutamate transporter. Cancer Res. 2003 Sep 1;63(17):5538-43.
39 The effect of low pH on breast cancer resistance protein (ABCG2)-mediated transport of methotrexate, 7-hydroxymethotrexate, methotrexate diglutamate, folic acid, mitoxantrone, topotecan, and resveratrol in in vitro drug transport models. Mol Pharmacol. 2007 Jan;71(1):240-9.
40 Role of BCRP as a biomarker for predicting resistance to 5-fluorouracil in breast cancer. Cancer Chemother Pharmacol. 2009 May;63(6):1103-10.
41 Inhibiting the function of ABCB1 and ABCG2 by the EGFR tyrosine kinase inhibitor AG1478. Biochem Pharmacol. 2009 Mar 1;77(5):781-93.
42 Sterol transport by the human breast cancer resistance protein (ABCG2) expressed in Lactococcus lactis. J Biol Chem. 2003 Jun 6;278(23):20645-51.
43 The phytoestrogen genistein enhances multidrug resistance in breast cancer cell lines by translational regulation of ABC transporters. Cancer Lett. 2016 Jun 28;376(1):165-72.
44 Curcumin inhibits the activity of ABCG2/BCRP1, a multidrug resistance-linked ABC drug transporter in mice. Pharm Res. 2009 Feb;26(2):480-7.
45 Imatinib mesylate (STI571) is a substrate for the breast cancer resistance protein (BCRP)/ABCG2 drug pump. Blood. 2004 Nov 1;104(9):2940-2.
46 Radium 223 dichloride for prostate cancer treatment. Drug Des Devel Ther. 2017 Sep 6;11:2643-2651.
47 Dose-ranging efficacy and safety study of ertugliflozin, a sodium-glucose co-transporter 2 inhibitor, in patients with type 2 diabetes on a background of metformin.Diabetes Obes Metab.2015 Jun;17(6):591-8.
48 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
49 LX4211, a dual SGLT1/SGLT2 inhibitor, improved glycemic control in patients with type 2 diabetes in a randomized, placebo-controlled trial. Clin Pharmacol Ther. 2012 Aug;92(2):158-69.
50 Ipragliflozin: A novel sodium-glucose cotransporter 2 inhibitor developed in Japan.World J Diabetes.2015 Feb 15;6(1):136-44.
51 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
52 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
53 Effects of AVE2268, a substituted glycopyranoside, on urinary glucose excretion and blood glucose in mice and rats. Arzneimittelforschung. 2008;58(11):574-80.
54 Pharmacological Characterization of YM543, a Newly Synthesized, Orally Active SGLT2 Selective Inhibitor. Endocr Res. 2013 Aug;38(3):168-183.
55 Cerner Multum, Inc. "UK Summary of Product Characteristics.".
56 Cerner Multum, Inc. "Australian Product Information.".
57 Product Information. Balversa (erdafitinib). Janssen Products, LP, Horsham, PA.
58 Product Information. Tukysa (tucatinib). Seattle Genetics Inc, Bothell, WA.
59 Product Information. Rukobia (fostemsavir). ViiV Healthcare, Research Triangle Park, NC.
60 Product Information. Nexletol (bempedoic acid). Esperion Therapeutics, Ann Arbor, MI.
61 Product Information. Tabrecta (capmatinib). Novartis Pharmaceuticals, East Hanover, NJ.
62 Product Information. Reyvow (lasmiditan). Lilly, Eli and Company, Indianapolis, IN.
63 Product Information. Nubeqa (darolutamide). Bayer HealthCare Pharmaceuticals Inc., Whippany, NJ.
64 Product Information. Tavalisse (fostamatinib). Rigel Pharmaceuticals, South San Francisco, CA.