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Identification
NameSaxagliptin
Accession NumberDB06335
TypeSmall Molecule
GroupsApproved
Description

Saxagliptin (rINN) is an orally active hypoglycemic (anti-diabetic drug) of the new dipeptidyl peptidase-4 (DPP-4) inhibitor class of drugs. FDA approved on July 31, 2009.

Structure
Thumb
Synonyms
(1S,3S,5S)-2-((2S)-Amino(3-hydroxytricyclo(3.3.1.13,7)dec-1-yl)acetyl)-2-azabicyclo(3.1.0)hexane-3-carbonitrile
BMS 477118
BMS-477118
Onglyza
External Identifiers
  • BMS-477118
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Onglyzatablet, film coated2.5 mg/1oralE.R. Squibb & Sons, L.L.C.2009-07-31Not applicableUs
Onglyzatablet, film coated5 mg/1oralCardinal Health2014-11-20Not applicableUs
Onglyzatablet, film coated5 mg/1oralCardinal Health2009-07-31Not applicableUs
Onglyzatablet, film coated5 mg/1oralPhysicians Total Care, Inc.2011-09-22Not applicableUs
Onglyzatablet, film coated5 mg/1oralAstra Zeneca Pharmaceuticals Lp2014-11-20Not applicableUs
Onglyzatablet, film coated2.5 mg/1oralAstra Zeneca Pharmaceuticals Lp2014-11-20Not applicableUs
Onglyzatablet2.5 mgoralAstrazeneca Canada Inc2011-12-23Not applicableCanada
Onglyzatablet, film coated5 mg/1oralE.R. Squibb & Sons, L.L.C.2009-07-31Not applicableUs
Onglyzatablet5 mgoralAstrazeneca Canada Inc2009-10-29Not applicableCanada
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixtures
NameLabellerIngredients
Kombiglyze XRE.R. Squibb & Sons, L.L.C.
KomboglyzeAstrazeneca Canada Inc
Salts
Name/CASStructureProperties
Saxagliptin Hydrochloride
Thumb
  • InChI Key: TUAZNHHHYVBVBR-NHKADLRUSA-N
  • Monoisotopic Mass: 351.171354798
  • Average Mass: 351.871
DBSALT000158
Categories
UNII8I7IO46IVQ
CAS number361442-04-8
WeightAverage: 315.41
Monoisotopic: 315.194677059
Chemical FormulaC18H25N3O2
InChI KeyInChIKey=QGJUIPDUBHWZPV-SGTAVMJGSA-N
InChI
InChI=1S/C18H25N3O2/c19-8-13-2-12-3-14(12)21(13)16(22)15(20)17-4-10-1-11(5-17)7-18(23,6-10)9-17/h10-15,23H,1-7,9,20H2/t10?,11?,12-,13+,14+,15-,17?,18?/m1/s1
IUPAC Name
(1S,3S,5S)-2-[(2S)-2-amino-2-(3-hydroxyadamantan-1-yl)acetyl]-2-azabicyclo[3.1.0]hexane-3-carbonitrile
SMILES
N[[email protected]](C(=O)N1[[email protected]]2C[[email protected]]2C[[email protected]]1C#N)C12CC3CC(CC(O)(C3)C1)C2
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as alpha amino acid amides. These are amide derivatives of alpha amino acids.
KingdomOrganic compounds
Super ClassOrganic acids and derivatives
ClassCarboxylic acids and derivatives
Sub ClassAmino acids, peptides, and analogues
Direct ParentAlpha amino acid amides
Alternative Parents
Substituents
  • Alpha-amino acid amide
  • N-acyl-piperidine
  • N-acylpyrrolidine
  • Piperidine
  • Tertiary carboxylic acid amide
  • Tertiary alcohol
  • Pyrrolidine
  • Cyclic alcohol
  • Tertiary amine
  • Carboxamide group
  • Azacycle
  • Organoheterocyclic compound
  • Nitrile
  • Carbonitrile
  • Hydrocarbon derivative
  • Primary amine
  • Organooxygen compound
  • Organonitrogen compound
  • Primary aliphatic amine
  • Carbonyl group
  • Amine
  • Alcohol
  • Aliphatic heteropolycyclic compound
Molecular FrameworkAliphatic heteropolycyclic compounds
External Descriptors
Pharmacology
IndicationTreatment of type 2 diabetes mellitus to improve glycemic control in combination with other agents or as monotherapy.
PharmacodynamicsPost-administration of saxagliptin, GLP-1 and GIP levels rise up to 2- to 3- fold. Because it is very selective of DPP-4 inhibition, there are fewer systemic side effects. Saxagliptin inhibits DPP-4 enzyme activity for a 24-hour period. It also decreased glucagon concentrations and increased glucose-dependent insulin secretion from pancreatic beta cells. The half maximal inhibitory concentration (IC50) is 0.5 nmol/L. Saxagliptin did not prolong the QTc interval to a clinically significant degree.
Mechanism of actionSaxagliptin is a dipeptidyl peptidase-4 (DPP-4) inhibitor antidiabetic for the treatment of type 2 diabetes. DPP-4 inhibitors are a class of compounds that work by affecting the action of natural hormones in the body called incretins. Incretins decrease blood sugar by increasing consumption of sugar by the body, mainly through increasing insulin production in the pancreas, and by reducing production of sugar by the liver. [Bristol-Myers Squibb Press Release] DPP-4 is a membrane associated peptidase which is found in many tissues, lymphocytes and plasma. DPP-4 has two main mechanisms of action, an enzymatic function and another mechanism where DPP-4 binds adenosine deaminase, which conveys intracellular signals via dimerization when activated. Saxagliptin forms a reversible, histidine-assisted covalent bond between its nitrile group and the S630 hydroxyl oxygen on DPP-4. The inhibition of DPP-4 increases levels active of glucagon like peptide 1 (GLP-1), which inhibits glucagon production from pancreatic alpha cells and increases production of insulin from pancreatic beta cells.
Related Articles
AbsorptionFollowing a 5 mg single oral dose of saxagliptin to healthy subjects, the mean plasma AUC values for saxagliptin and its active metabolite were 78 ng•h/mL and 214 ng•h/mL, respectively. The corresponding plasma Cmax values were 24 ng/mL and 47 ng/mL, respectively. Saxagliptin did not accumulate following repeated doses. The median time to maximum concentration (Tmax) following the 5 mg once daily dose was 2 hours for saxagliptin and 4 hours for its active metabolite. Bioavailability, 2.5 - 50 mg dose = 67%
Volume of distribution

151 L

Protein bindingThe in vitro protein binding of saxagliptin and its active metabolite in human serum is negligible (<10%).
Metabolism

The metabolism of saxagliptin is primarily mediated by cytochrome P450 3A4/5 (CYP3A4/5). 50% of the absorbed dose will undergo hepatic metabolism. The major metabolite of saxagliptin, 5-hydroxy saxagliptin, is also a DPP4 inhibitor, which is one-half as potent as saxagliptin.

SubstrateEnzymesProduct
Saxagliptin
5-hydroxy saxagliptinDetails
Route of eliminationSaxagliptin is eliminated by both renal and hepatic pathways. Following a single 50 mg dose of 14C-saxagliptin, 24%, 36%, and 75% of the dose was excreted in the urine as saxagliptin, its active metabolite, and total radioactivity, respectively. A total of 22% of the administered radioactivity was recovered in feces representing the fraction of the saxagliptin dose excreted in bile and/or unabsorbed drug from the gastrointestinal tract.
Half lifeSaxagliptin = 2.5 hours; 5-hydroxy saxagliptin = 3.1 hours;
Clearance

Renal clearance, single 50 mg dose = 14 L/h

ToxicityAdverse reactions reported in ≥5% of patients treated with saxagliptin and more commonly than in patients treated with placebo are: upper respiratory tract infection, urinary tract infection, and headache.
Affected organismsNot Available
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9894
Blood Brain Barrier+0.8823
Caco-2 permeable-0.5446
P-glycoprotein substrateSubstrate0.5909
P-glycoprotein inhibitor INon-inhibitor0.696
P-glycoprotein inhibitor IINon-inhibitor0.7875
Renal organic cation transporterNon-inhibitor0.7903
CYP450 2C9 substrateNon-substrate0.8618
CYP450 2D6 substrateNon-substrate0.7519
CYP450 3A4 substrateSubstrate0.5944
CYP450 1A2 substrateNon-inhibitor0.8448
CYP450 2C9 inhibitorNon-inhibitor0.8017
CYP450 2D6 inhibitorNon-inhibitor0.8198
CYP450 2C19 inhibitorNon-inhibitor0.81
CYP450 3A4 inhibitorNon-inhibitor0.8641
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9032
Ames testNon AMES toxic0.7569
CarcinogenicityNon-carcinogens0.9122
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.7529 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9912
hERG inhibition (predictor II)Non-inhibitor0.832
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
Tablet, film coated, extended releaseoral
Tabletoral
Tabletoral2.5 mg
Tabletoral5 mg
Tablet, film coatedoral2.5 mg/1
Tablet, film coatedoral5 mg/1
PricesNot Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US6395767 No2001-02-162021-02-16Us
US7951400 No2008-11-302028-11-30Us
US8628799 No2005-07-132025-07-13Us
USRE44186 No2003-07-312023-07-31Us
Properties
StateSolid
Experimental Properties
PropertyValueSource
water solubilitySparingly solubleFDA label
Predicted Properties
PropertyValueSource
Water Solubility2.26 mg/mLALOGPS
logP0.88ALOGPS
logP-0.08ChemAxon
logS-2.1ALOGPS
pKa (Strongest Acidic)14.74ChemAxon
pKa (Strongest Basic)7.9ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area90.35 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity83.99 m3·mol-1ChemAxon
Polarizability34.22 Å3ChemAxon
Number of Rings5ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
References
Synthesis Reference

Jack Z. Gougoutas, Mary F. Malley, John D. DiMarco, Xiaotian S. Yin, Chenkou Wei, Jurong Yu, Truc Chi Vu, Gregory Scott Jones, Scott A. Savage, “CRYSTAL FORMS OF SAXAGLIPTIN AND PROCESSES FOR PREPARING SAME.” U.S. Patent US20090054303, issued February 26, 2009.

US20090054303
General References
  1. Rosenstock J, Sankoh S, List JF: Glucose-lowering activity of the dipeptidyl peptidase-4 inhibitor saxagliptin in drug-naive patients with type 2 diabetes. Diabetes Obes Metab. 2008 May;10(5):376-86. doi: 10.1111/j.1463-1326.2008.00876.x. Epub 2008 Mar 18. [PubMed:18355324 ]
  2. Metzler WJ, Yanchunas J, Weigelt C, Kish K, Klei HE, Xie D, Zhang Y, Corbett M, Tamura JK, He B, Hamann LG, Kirby MS, Marcinkeviciene J: Involvement of DPP-IV catalytic residues in enzyme-saxagliptin complex formation. Protein Sci. 2008 Feb;17(2):240-50. doi: 10.1110/ps.073253208. [PubMed:18227430 ]
  3. Crepaldi G, Carruba M, Comaschi M, Del Prato S, Frajese G, Paolisso G: Dipeptidyl peptidase 4 (DPP-4) inhibitors and their role in Type 2 diabetes management. J Endocrinol Invest. 2007 Jul-Aug;30(7):610-4. [PubMed:17848846 ]
  4. Barnett A: DPP-4 inhibitors and their potential role in the management of type 2 diabetes. Int J Clin Pract. 2006 Nov;60(11):1454-70. [PubMed:17073841 ]
  5. Kulasa K, Edelman S: Saxagliptin: the evidence for its place in the treatment of type 2 diabetes mellitus. Core Evid. 2010 Oct 21;5:23-37. [PubMed:21042540 ]
  6. Russell S: Incretin-based therapies for type 2 diabetes mellitus: a review of direct comparisons of efficacy, safety and patient satisfaction. Int J Clin Pharm. 2013 Apr;35(2):159-72. doi: 10.1007/s11096-012-9729-9. Epub 2012 Dec 22. [PubMed:23263796 ]
  7. Ali S, Fonseca V: Saxagliptin overview: special focus on safety and adverse effects. Expert Opin Drug Saf. 2013 Jan;12(1):103-9. doi: 10.1517/14740338.2013.741584. Epub 2012 Nov 9. [PubMed:23137182 ]
  8. Golightly LK, Drayna CC, McDermott MT: Comparative clinical pharmacokinetics of dipeptidyl peptidase-4 inhibitors. Clin Pharmacokinet. 2012 Aug 1;51(8):501-14. doi: 10.2165/11632930-000000000-00000. [PubMed:22686547 ]
External Links
ATC CodesA10BD10A10BH03A10BD21
AHFS Codes
  • 68:20.05
PDB EntriesNot Available
FDA labelDownload (492 KB)
MSDSDownload (479 KB)
Interactions
Drug Interactions
Drug
Acetylsalicylic acidAcetylsalicylic acid may increase the hypoglycemic activities of Saxagliptin.
AprepitantThe serum concentration of Saxagliptin can be increased when it is combined with Aprepitant.
AripiprazoleThe therapeutic efficacy of Saxagliptin can be decreased when used in combination with Aripiprazole.
ArmodafinilThe serum concentration of Saxagliptin can be decreased when it is combined with Armodafinil.
Arsenic trioxideThe therapeutic efficacy of Saxagliptin can be decreased when used in combination with Arsenic trioxide.
ArticaineThe therapeutic efficacy of Saxagliptin can be decreased when used in combination with Articaine.
AsenapineThe therapeutic efficacy of Saxagliptin can be decreased when used in combination with Asenapine.
AtazanavirThe therapeutic efficacy of Saxagliptin can be decreased when used in combination with Atazanavir.
BendroflumethiazideThe therapeutic efficacy of Saxagliptin can be decreased when used in combination with Bendroflumethiazide.
BetamethasoneThe therapeutic efficacy of Saxagliptin can be decreased when used in combination with Betamethasone.
BexaroteneThe serum concentration of Saxagliptin can be decreased when it is combined with Bexarotene.
BoceprevirThe serum concentration of Saxagliptin can be increased when it is combined with Boceprevir.
BosentanThe serum concentration of Saxagliptin can be decreased when it is combined with Bosentan.
BrexpiprazoleThe therapeutic efficacy of Saxagliptin can be decreased when used in combination with Brexpiprazole.
BumetanideThe therapeutic efficacy of Saxagliptin can be decreased when used in combination with Bumetanide.
BuserelinThe therapeutic efficacy of Saxagliptin can be decreased when used in combination with Buserelin.
CalcitriolThe serum concentration of Saxagliptin can be decreased when it is combined with Calcitriol.
CarbamazepineThe serum concentration of Saxagliptin can be decreased when it is combined with Carbamazepine.
CeritinibThe therapeutic efficacy of Saxagliptin can be decreased when used in combination with Ceritinib.
ChlorothiazideThe therapeutic efficacy of Saxagliptin can be decreased when used in combination with Chlorothiazide.
ChlorpropamideSaxagliptin may increase the hypoglycemic activities of Chlorpropamide.
ChlorthalidoneThe therapeutic efficacy of Saxagliptin can be decreased when used in combination with Chlorthalidone.
ClarithromycinThe serum concentration of Saxagliptin can be increased when it is combined with Clarithromycin.
ClobazamThe serum concentration of Saxagliptin can be decreased when it is combined with Clobazam.
ClozapineThe therapeutic efficacy of Saxagliptin can be decreased when used in combination with Clozapine.
CobicistatThe serum concentration of Saxagliptin can be increased when it is combined with Cobicistat.
ConivaptanThe serum concentration of Saxagliptin can be increased when it is combined with Conivaptan.
CorticotropinThe therapeutic efficacy of Saxagliptin can be decreased when used in combination with Corticotropin.
Cortisone acetateThe therapeutic efficacy of Saxagliptin can be decreased when used in combination with Cortisone acetate.
CrizotinibThe serum concentration of Saxagliptin can be increased when it is combined with Crizotinib.
Cyproterone acetateThe therapeutic efficacy of Saxagliptin can be decreased when used in combination with Cyproterone acetate.
DabrafenibThe serum concentration of Saxagliptin can be decreased when it is combined with Dabrafenib.
DanazolThe therapeutic efficacy of Saxagliptin can be decreased when used in combination with Danazol.
DarunavirThe therapeutic efficacy of Saxagliptin can be decreased when used in combination with Darunavir.
DasatinibThe serum concentration of Saxagliptin can be increased when it is combined with Dasatinib.
DeferasiroxThe serum concentration of Saxagliptin can be decreased when it is combined with Deferasirox.
DelavirdineThe serum concentration of Saxagliptin can be increased when it is combined with Delavirdine.
DesogestrelThe therapeutic efficacy of Saxagliptin can be decreased when used in combination with Desogestrel.
DesvenlafaxineThe serum concentration of Saxagliptin can be decreased when it is combined with Desvenlafaxine.
DexamethasoneThe serum concentration of Saxagliptin can be decreased when it is combined with Dexamethasone.
DiazoxideThe therapeutic efficacy of Saxagliptin can be decreased when used in combination with Diazoxide.
DicloxacillinThe serum concentration of Saxagliptin can be decreased when it is combined with Dicloxacillin.
DienogestThe therapeutic efficacy of Saxagliptin can be decreased when used in combination with Dienogest.
DihydrotestosteroneDihydrotestosterone may increase the hypoglycemic activities of Saxagliptin.
DiltiazemThe serum concentration of Saxagliptin can be increased when it is combined with Diltiazem.
DisopyramideSaxagliptin may increase the hypoglycemic activities of Disopyramide.
DronedaroneThe serum concentration of Saxagliptin can be increased when it is combined with Dronedarone.
DrospirenoneThe therapeutic efficacy of Saxagliptin can be decreased when used in combination with Drospirenone.
EfavirenzThe serum concentration of Saxagliptin can be decreased when it is combined with Efavirenz.
EnzalutamideThe serum concentration of Saxagliptin can be decreased when it is combined with Enzalutamide.
EpinephrineThe therapeutic efficacy of Saxagliptin can be decreased when used in combination with Epinephrine.
ErythromycinThe serum concentration of Saxagliptin can be increased when it is combined with Erythromycin.
Eslicarbazepine acetateThe serum concentration of Saxagliptin can be decreased when it is combined with Eslicarbazepine acetate.
EstradiolThe serum concentration of Saxagliptin can be decreased when it is combined with Estradiol.
Estrone sulfateThe therapeutic efficacy of Saxagliptin can be decreased when used in combination with Estropipate.
Etacrynic acidThe therapeutic efficacy of Saxagliptin can be decreased when used in combination with Ethacrynic acid.
Ethinyl EstradiolThe therapeutic efficacy of Saxagliptin can be decreased when used in combination with Ethinyl Estradiol.
Ethynodiol diacetateThe therapeutic efficacy of Saxagliptin can be decreased when used in combination with Ethynodiol.
EtonogestrelThe therapeutic efficacy of Saxagliptin can be decreased when used in combination with Etonogestrel.
EtravirineThe serum concentration of Saxagliptin can be decreased when it is combined with Etravirine.
EverolimusThe therapeutic efficacy of Saxagliptin can be decreased when used in combination with Everolimus.
ExemestaneThe serum concentration of Saxagliptin can be decreased when it is combined with Exemestane.
FelbamateThe serum concentration of Saxagliptin can be decreased when it is combined with Felbamate.
FluconazoleThe serum concentration of Saxagliptin can be increased when it is combined with Fluconazole.
FludrocortisoneThe therapeutic efficacy of Saxagliptin can be decreased when used in combination with Fludrocortisone.
FosamprenavirThe serum concentration of Saxagliptin can be increased when it is combined with Fosamprenavir.
FosaprepitantThe serum concentration of Saxagliptin can be increased when it is combined with Fosaprepitant.
FosphenytoinThe serum concentration of Saxagliptin can be decreased when it is combined with Fosphenytoin.
FurosemideThe therapeutic efficacy of Saxagliptin can be decreased when used in combination with Furosemide.
Fusidic AcidThe serum concentration of Saxagliptin can be increased when it is combined with Fusidic Acid.
GliclazideSaxagliptin may increase the hypoglycemic activities of Gliclazide.
GlimepirideSaxagliptin may increase the hypoglycemic activities of Glimepiride.
GlipizideSaxagliptin may increase the hypoglycemic activities of Glipizide.
GlyburideSaxagliptin may increase the hypoglycemic activities of Glyburide.
GoserelinThe therapeutic efficacy of Saxagliptin can be decreased when used in combination with Goserelin.
GriseofulvinThe serum concentration of Saxagliptin can be decreased when it is combined with Griseofulvin.
HistrelinThe therapeutic efficacy of Saxagliptin can be decreased when used in combination with Histrelin.
HydrochlorothiazideThe therapeutic efficacy of Saxagliptin can be decreased when used in combination with Hydrochlorothiazide.
HydrocortisoneThe serum concentration of Saxagliptin can be decreased when it is combined with Hydrocortisone.
Hydroxyprogesterone caproateThe therapeutic efficacy of Saxagliptin can be decreased when used in combination with Hydroxyprogesterone caproate.
IdelalisibThe serum concentration of Saxagliptin can be increased when it is combined with Idelalisib.
IloperidoneThe therapeutic efficacy of Saxagliptin can be decreased when used in combination with Iloperidone.
ImatinibThe serum concentration of Saxagliptin can be increased when it is combined with Imatinib.
IndapamideThe therapeutic efficacy of Saxagliptin can be decreased when used in combination with Indapamide.
IndinavirThe therapeutic efficacy of Saxagliptin can be decreased when used in combination with Indinavir.
Insulin AspartSaxagliptin may increase the hypoglycemic activities of Insulin Aspart.
Insulin DegludecSaxagliptin may increase the hypoglycemic activities of Insulin degludec.
Insulin DetemirSaxagliptin may increase the hypoglycemic activities of Insulin Detemir.
Insulin GlargineSaxagliptin may increase the hypoglycemic activities of Insulin Glargine.
Insulin GlulisineSaxagliptin may increase the hypoglycemic activities of Insulin Glulisine.
Insulin HumanSaxagliptin may increase the hypoglycemic activities of Insulin Regular.
Insulin LisproSaxagliptin may increase the hypoglycemic activities of Insulin Lispro.
IsavuconazoniumThe serum concentration of Saxagliptin can be decreased when it is combined with Isavuconazonium.
ItraconazoleThe serum concentration of Saxagliptin can be increased when it is combined with Itraconazole.
IvacaftorThe serum concentration of Saxagliptin can be increased when it is combined with Ivacaftor.
KetoconazoleThe serum concentration of Saxagliptin can be increased when it is combined with Ketoconazole.
LanreotideSaxagliptin may increase the hypoglycemic activities of Lanreotide.
LeuprolideThe therapeutic efficacy of Saxagliptin can be decreased when used in combination with Leuprolide.
LevonorgestrelThe therapeutic efficacy of Saxagliptin can be decreased when used in combination with Levonorgestrel.
Lipoic AcidLipoic Acid may increase the hypoglycemic activities of Saxagliptin.
LopinavirThe therapeutic efficacy of Saxagliptin can be decreased when used in combination with Lopinavir.
LuliconazoleThe serum concentration of Saxagliptin can be increased when it is combined with Luliconazole.
LumacaftorThe serum concentration of Saxagliptin can be decreased when it is combined with Lumacaftor.
LurasidoneThe therapeutic efficacy of Saxagliptin can be decreased when used in combination with Lurasidone.
MecaserminSaxagliptin may increase the hypoglycemic activities of Mecasermin.
Medroxyprogesterone acetateThe serum concentration of Saxagliptin can be decreased when it is combined with Medroxyprogesterone Acetate.
Megestrol acetateThe therapeutic efficacy of Saxagliptin can be decreased when used in combination with Megestrol acetate.
MestranolThe therapeutic efficacy of Saxagliptin can be decreased when used in combination with Mestranol.
MethotrimeprazineThe therapeutic efficacy of Saxagliptin can be decreased when used in combination with Methotrimeprazine.
MethyclothiazideThe therapeutic efficacy of Saxagliptin can be decreased when used in combination with Methyclothiazide.
MethylprednisoloneThe therapeutic efficacy of Saxagliptin can be decreased when used in combination with Methylprednisolone.
MetolazoneThe therapeutic efficacy of Saxagliptin can be decreased when used in combination with Metolazone.
MetyraponeThe serum concentration of Saxagliptin can be decreased when it is combined with Metyrapone.
MifepristoneThe serum concentration of Saxagliptin can be increased when it is combined with Mifepristone.
MitotaneThe serum concentration of Saxagliptin can be decreased when it is combined with Mitotane.
ModafinilThe serum concentration of Saxagliptin can be decreased when it is combined with Modafinil.
NadololThe therapeutic efficacy of Saxagliptin can be decreased when used in combination with Nadolol.
NafcillinThe serum concentration of Saxagliptin can be decreased when it is combined with Nafcillin.
NateglinideSaxagliptin may increase the hypoglycemic activities of Nateglinide.
NefazodoneThe serum concentration of Saxagliptin can be increased when it is combined with Nefazodone.
NelfinavirThe therapeutic efficacy of Saxagliptin can be decreased when used in combination with Nelfinavir.
NetupitantThe serum concentration of Saxagliptin can be increased when it is combined with Netupitant.
NevirapineThe serum concentration of Saxagliptin can be decreased when it is combined with Nevirapine.
NiacinThe therapeutic efficacy of Saxagliptin can be decreased when used in combination with Niacin.
NilotinibThe serum concentration of Saxagliptin can be increased when it is combined with Nilotinib.
NorethisteroneThe therapeutic efficacy of Saxagliptin can be decreased when used in combination with Norethindrone.
NorgestimateThe therapeutic efficacy of Saxagliptin can be decreased when used in combination with Norgestimate.
OctreotideSaxagliptin may increase the hypoglycemic activities of Octreotide.
OlanzapineThe therapeutic efficacy of Saxagliptin can be decreased when used in combination with Olanzapine.
OritavancinThe serum concentration of Saxagliptin can be decreased when it is combined with Oritavancin.
OxandroloneOxandrolone may increase the hypoglycemic activities of Saxagliptin.
OxcarbazepineThe serum concentration of Saxagliptin can be decreased when it is combined with Oxcarbazepine.
PaclitaxelThe serum concentration of Saxagliptin can be decreased when it is combined with Paclitaxel.
PalbociclibThe serum concentration of Saxagliptin can be increased when it is combined with Palbociclib.
PaliperidoneThe therapeutic efficacy of Saxagliptin can be decreased when used in combination with Paliperidone.
PantoprazoleThe serum concentration of Saxagliptin can be decreased when it is combined with Pantoprazole.
ParoxetineParoxetine may increase the hypoglycemic activities of Saxagliptin.
PasireotideSaxagliptin may increase the hypoglycemic activities of Pasireotide.
PegvisomantPegvisomant may increase the hypoglycemic activities of Saxagliptin.
PentamidineSaxagliptin may increase the hypoglycemic activities of Pentamidine.
PerampanelThe serum concentration of Saxagliptin can be decreased when it is combined with Perampanel.
PerindoprilThe risk or severity of adverse effects can be increased when Saxagliptin is combined with Perindopril.
PhenelzinePhenelzine may increase the hypoglycemic activities of Saxagliptin.
PhenobarbitalThe serum concentration of Saxagliptin can be decreased when it is combined with Phenobarbital.
PhenytoinThe serum concentration of Saxagliptin can be decreased when it is combined with Phenytoin.
PioglitazoneThe serum concentration of Saxagliptin can be decreased when it is combined with Pioglitazone.
PipotiazineThe therapeutic efficacy of Saxagliptin can be decreased when used in combination with Pipotiazine.
PosaconazoleThe serum concentration of Saxagliptin can be increased when it is combined with Posaconazole.
PrednisoloneThe therapeutic efficacy of Saxagliptin can be decreased when used in combination with Prednisolone.
PrednisoneThe serum concentration of Saxagliptin can be decreased when it is combined with Prednisone.
PrimidoneThe serum concentration of Saxagliptin can be decreased when it is combined with Primidone.
ProgesteroneThe therapeutic efficacy of Saxagliptin can be decreased when used in combination with Progesterone.
QuetiapineThe therapeutic efficacy of Saxagliptin can be decreased when used in combination with Quetiapine.
QuinineSaxagliptin may increase the hypoglycemic activities of Quinine.
RanolazineThe serum concentration of Saxagliptin can be increased when it is combined with Ranolazine.
RepaglinideSaxagliptin may increase the hypoglycemic activities of Repaglinide.
Repository corticotropinThe therapeutic efficacy of Saxagliptin can be decreased when used in combination with Repository corticotropin.
RifabutinThe serum concentration of Saxagliptin can be decreased when it is combined with Rifabutin.
RifampicinThe serum concentration of Saxagliptin can be decreased when it is combined with Rifampicin.
RifapentineThe serum concentration of Saxagliptin can be decreased when it is combined with Rifapentine.
RisperidoneThe therapeutic efficacy of Saxagliptin can be decreased when used in combination with Risperidone.
RitonavirThe therapeutic efficacy of Saxagliptin can be decreased when used in combination with Ritonavir.
RufinamideThe serum concentration of Saxagliptin can be decreased when it is combined with Rufinamide.
SaquinavirThe therapeutic efficacy of Saxagliptin can be decreased when used in combination with Saquinavir.
SimeprevirThe serum concentration of Saxagliptin can be increased when it is combined with Simeprevir.
SirolimusThe therapeutic efficacy of Saxagliptin can be decreased when used in combination with Sirolimus.
SparfloxacinSparfloxacin may increase the hypoglycemic activities of Saxagliptin.
StiripentolThe serum concentration of Saxagliptin can be increased when it is combined with Stiripentol.
SulfadiazineSaxagliptin may increase the hypoglycemic activities of Sulfadiazine.
SulfamethoxazoleSaxagliptin may increase the hypoglycemic activities of Sulfamethoxazole.
SulfisoxazoleSaxagliptin may increase the hypoglycemic activities of Sulfisoxazole.
SunitinibSaxagliptin may increase the hypoglycemic activities of Sunitinib.
TacrolimusThe therapeutic efficacy of Saxagliptin can be decreased when used in combination with Tacrolimus.
TelaprevirThe serum concentration of Saxagliptin can be increased when it is combined with Telaprevir.
TelithromycinThe serum concentration of Saxagliptin can be increased when it is combined with Telithromycin.
TemsirolimusThe therapeutic efficacy of Saxagliptin can be decreased when used in combination with Temsirolimus.
TerbinafineThe serum concentration of Saxagliptin can be decreased when it is combined with Terbinafine.
TesmilifeneThe serum concentration of Saxagliptin can be decreased when it is combined with Tesmilifene.
TestosteroneTestosterone may increase the hypoglycemic activities of Saxagliptin.
TipranavirThe therapeutic efficacy of Saxagliptin can be decreased when used in combination with Tipranavir.
TolazamideSaxagliptin may increase the hypoglycemic activities of Tolazamide.
TolbutamideSaxagliptin may increase the hypoglycemic activities of Tolbutamide.
TopiramateThe serum concentration of Saxagliptin can be decreased when it is combined with Topiramate.
TorasemideThe therapeutic efficacy of Saxagliptin can be decreased when used in combination with Torasemide.
TrametinibThe serum concentration of Saxagliptin can be decreased when it is combined with Trametinib.
TranylcypromineTranylcypromine may increase the hypoglycemic activities of Saxagliptin.
TriamcinoloneThe therapeutic efficacy of Saxagliptin can be decreased when used in combination with Triamcinolone.
TrichlormethiazideThe therapeutic efficacy of Saxagliptin can be decreased when used in combination with Trichlormethiazide.
TrimethoprimSaxagliptin may increase the hypoglycemic activities of Trimethoprim.
TriptorelinThe therapeutic efficacy of Saxagliptin can be decreased when used in combination with Triptorelin.
VemurafenibThe serum concentration of Saxagliptin can be decreased when it is combined with Vemurafenib.
VerapamilThe serum concentration of Saxagliptin can be increased when it is combined with Verapamil.
VoriconazoleThe serum concentration of Saxagliptin can be increased when it is combined with Voriconazole.
VorinostatThe therapeutic efficacy of Saxagliptin can be decreased when used in combination with Vorinostat.
ZiprasidoneThe therapeutic efficacy of Saxagliptin can be decreased when used in combination with Ziprasidone.
Food Interactions
  • Administration with a high-fat meal resulted in an increase in Tmax of saxagliptin by approximately 20 minutes as compared to fasted conditions. There was a 27% increase in the AUC of saxagliptin when given with a meal as compared to fasted conditions.

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Virus receptor activity
Specific Function:
Cell surface glycoprotein receptor involved in the costimulatory signal essential for T-cell receptor (TCR)-mediated T-cell activation. Acts as a positive regulator of T-cell coactivation, by binding at least ADA, CAV1, IGF2R, and PTPRC. Its binding to CAV1 and CARD11 induces T-cell proliferation and NF-kappa-B activation in a T-cell receptor/CD3-dependent manner. Its interaction with ADA also ...
Gene Name:
DPP4
Uniprot ID:
P27487
Molecular Weight:
88277.935 Da
References
  1. Augeri DJ, Robl JA, Betebenner DA, Magnin DR, Khanna A, Robertson JG, Wang A, Simpkins LM, Taunk P, Huang Q, Han SP, Abboa-Offei B, Cap M, Xin L, Tao L, Tozzo E, Welzel GE, Egan DM, Marcinkeviciene J, Chang SY, Biller SA, Kirby MS, Parker RA, Hamann LG: Discovery and preclinical profile of Saxagliptin (BMS-477118): a highly potent, long-acting, orally active dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes. J Med Chem. 2005 Jul 28;48(15):5025-37. [PubMed:16033281 ]

Enzymes

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 reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiot...
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular Weight:
57342.67 Da
References
  1. Upreti VV, Boulton DW, Li L, Ching A, Su H, Lacreta FP, Patel CG: Effect of rifampicin on the pharmacokinetics and pharmacodynamics of saxagliptin, a dipeptidyl peptidase-4 inhibitor, in healthy subjects. Br J Clin Pharmacol. 2011 Jul;72(1):92-102. doi: 10.1111/j.1365-2125.2011.03937.x. [PubMed:21651615 ]
  2. Patel CG, Kornhauser D, Vachharajani N, Komoroski B, Brenner E, Handschuh del Corral M, Li L, Boulton DW: Saxagliptin, a potent, selective inhibitor of DPP-4, does not alter the pharmacokinetics of three oral antidiabetic drugs (metformin, glyburide or pioglitazone) in healthy subjects. Diabetes Obes Metab. 2011 Jul;13(7):604-14. doi: 10.1111/j.1463-1326.2011.01381.x. [PubMed:21332626 ]
  3. Scheen AJ: Dipeptidylpeptidase-4 inhibitors (gliptins): focus on drug-drug interactions. Clin Pharmacokinet. 2010 Sep;49(9):573-88. doi: 10.2165/11532980-000000000-00000. [PubMed:20690781 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Oxygen binding
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 unrelated compounds, including steroids, fatty acids, and xenobiotics.
Gene Name:
CYP3A5
Uniprot ID:
P20815
Molecular Weight:
57108.065 Da
References
  1. Upreti VV, Boulton DW, Li L, Ching A, Su H, Lacreta FP, Patel CG: Effect of rifampicin on the pharmacokinetics and pharmacodynamics of saxagliptin, a dipeptidyl peptidase-4 inhibitor, in healthy subjects. Br J Clin Pharmacol. 2011 Jul;72(1):92-102. doi: 10.1111/j.1365-2125.2011.03937.x. [PubMed:21651615 ]
  2. Patel CG, Kornhauser D, Vachharajani N, Komoroski B, Brenner E, Handschuh del Corral M, Li L, Boulton DW: Saxagliptin, a potent, selective inhibitor of DPP-4, does not alter the pharmacokinetics of three oral antidiabetic drugs (metformin, glyburide or pioglitazone) in healthy subjects. Diabetes Obes Metab. 2011 Jul;13(7):604-14. doi: 10.1111/j.1463-1326.2011.01381.x. [PubMed:21332626 ]
  3. Scheen AJ: Dipeptidylpeptidase-4 inhibitors (gliptins): focus on drug-drug interactions. Clin Pharmacokinet. 2010 Sep;49(9):573-88. doi: 10.2165/11532980-000000000-00000. [PubMed:20690781 ]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Transporter activity
Specific Function:
Mediates export of organic anions and drugs from the cytoplasm. Mediates ATP-dependent transport of glutathione and glutathione conjugates, leukotriene C4, estradiol-17-beta-o-glucuronide, methotrexate, antiviral drugs and other xenobiotics. Confers resistance to anticancer drugs. Hydrolyzes ATP with low efficiency.
Gene Name:
ABCC1
Uniprot ID:
P33527
Molecular Weight:
171589.5 Da
References
  1. Scheen AJ: Dipeptidylpeptidase-4 inhibitors (gliptins): focus on drug-drug interactions. Clin Pharmacokinet. 2010 Sep;49(9):573-88. doi: 10.2165/11532980-000000000-00000. [PubMed:20690781 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Sodium-independent organic anion transmembrane transporter activity
Specific Function:
Organic anion transporter, capable of transporting pharmacological substances such as digoxin, ouabain, thyroxine, methotrexate and cAMP. May participate in the regulation of membrane transport of ouabain. Involved in the uptake of the dipeptidyl peptidase-4 inhibitor sitagliptin and hence may play a role in its transport into and out of renal proximal tubule cells. May be involved in the first...
Gene Name:
SLCO4C1
Uniprot ID:
Q6ZQN7
Molecular Weight:
78947.525 Da
References
  1. Golightly LK, Drayna CC, McDermott MT: Comparative clinical pharmacokinetics of dipeptidyl peptidase-4 inhibitors. Clin Pharmacokinet. 2012 Aug 1;51(8):501-14. doi: 10.2165/11632930-000000000-00000. [PubMed:22686547 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Sodium-independent organic anion transmembrane transporter activity
Specific Function:
Plays an important role in the excretion/detoxification of endogenous and exogenous organic anions, especially from the brain and kidney. Involved in the transport basolateral of steviol, fexofenadine. Transports benzylpenicillin (PCG), estrone-3-sulfate (E1S), cimetidine (CMD), 2,4-dichloro-phenoxyacetate (2,4-D), p-amino-hippurate (PAH), acyclovir (ACV) and ochratoxin (OTA).
Gene Name:
SLC22A8
Uniprot ID:
Q8TCC7
Molecular Weight:
59855.585 Da
References
  1. Golightly LK, Drayna CC, McDermott MT: Comparative clinical pharmacokinetics of dipeptidyl peptidase-4 inhibitors. Clin Pharmacokinet. 2012 Aug 1;51(8):501-14. doi: 10.2165/11632930-000000000-00000. [PubMed:22686547 ]
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Drug created on March 19, 2008 10:24 / Updated on August 24, 2016 01:52