Identification
- Summary
Alogliptin is a dipeptidyl peptidase-4 (DPP-4) inhibitor used to treat hyperglycemia in patients with type 2 diabetes mellitus.
- Brand Names
- Incresync, Kazano, Nesina, Oseni
- Generic Name
- Alogliptin
- DrugBank Accession Number
- DB06203
- Background
Alogliptin is a selective, orally-bioavailable inhibitor of enzymatic activity of dipeptidyl peptidase-4 (DPP-4). Chemically, alogliptin is prepared as a benzoate salt and exists predominantly as the R-enantiomer (>99%). It undergoes little or no chiral conversion in vivo to the (S)-enantiomer. FDA approved January 25, 2013.
- Type
- Small Molecule
- Groups
- Approved
- Structure
Structure for Alogliptin (DB06203)
- Weight
- Average: 339.3916
Monoisotopic: 339.169524941 - Chemical Formula
- C18H21N5O2
- Synonyms
- Alogliptin
- Alogliptina
- Alogliptine
- Alogliptinum
Pharmacology
- Indication
Indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Used as adjunct in combination to manage Type 2 diabetes mellitus Combination Product in combination with: Pioglitazone (DB01132) •••••••••••• Used as adjunct in combination to manage Type 2 diabetes mellitus Combination Product in combination with: Metformin (DB00331) •••••••••••• Management of Type 2 diabetes mellitus •••••••••••• - Contraindications & Blackbox Warnings
Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- Pharmacodynamics
Peak inhibition of DPP-4 occurs within 2-3 hours after a single-dose administration to healthy subjects. The peak inhibition of DPP-4 exceeded 93% across doses of 12.5 mg to 800 mg. Inhibition of DPP-4 remained above 80% at 24 hours for doses greater than or equal to 25 mg. Alogliptin also demonstrated decreases in postprandial glucagon while increasing postprandial active GLP-1 levels compared to placebo over an 8-hour period following a standardized meal. Alogliptin does not affect the QTc interval.
- Mechanism of action
Alogliptin inhibits dipeptidyl peptidase 4 (DPP-4), which normally degrades the incretins glucose-dependent insulinotropic polypeptide (GIP) and glucagon like peptide 1 ( GLP-1). The inhibition of DPP-4 increases the amount of active plasma incretins which helps with glycemic control. GIP and GLP-1 stimulate glucose dependent secretion of insulin in pancreatic beta cells. GLP-1 has the additional effects of suppressing glucose dependent glucagon secretion, inducing satiety, reducing food intake, and reducing gastric emptying.
Target Actions Organism ADipeptidyl peptidase 4 inhibitorHumans - Absorption
The pharmacokinetics of NESINA was also shown to be similar in healthy subjects and in patients with type 2 diabetes. When single, oral doses up to 800 mg in healthy subjects and type 2 diabetes patients are given, the peak plasma alogliptin concentration (median Tmax) occurred 1 to 2 hours after dosing. Accumulation of aloglipin is minimal. The absolute bioavailability of NESINA is approximately 100%. Food does not affect the absorption of alogliptin.
- Volume of distribution
Following a single, 12.5 mg intravenous infusion of alogliptin to healthy subjects, the volume of distribution during the terminal phase was 417 L, indicating that the drug is well distributed into tissues.
- Protein binding
Alogliptin is 20% bound to plasma proteins.
- Metabolism
Alogliptin does not undergo extensive metabolism. Two minor metabolites that were detected are N-demethylated alogliptin (<1% of parent compound) and N-acetylated alogliptin (<6% of parent compound). The N-demethylated metabolite is active and an inhibitor of DPP-4. The N-acetylated metabolite is inactive. Cytochrome enzymes that are involved with the metabolism of alogliptin are CYP2D6 and CYP3A4 but the extent to which this occurs is minimal. Approximately 10-20% of the dose is hepatically metabolized by cytochrome enzymes.
- Route of elimination
Renal excretion (76%) and feces (13%). 60% to 71% of the dose is excreted as unchanged drug in the urine.
- Half-life
Terminal half-life = 21 hours
- Clearance
Renal clearance = 9.6 L/h (this value indicates some active renal tubular secretion); Systemic clearance = 14.0 L/h.
- Adverse Effects
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Common adverse reactions (reported in ≥4% of patients treated with alogliptin 25 mg and more frequently than in patients who received placebo) are: nasopharyngitis, headache, and upper respiratory tract infection.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- 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.
Drug Interaction Integrate drug-drug
interactions in your softwareAbacavir Abacavir may decrease the excretion rate of Alogliptin which could result in a higher serum level. Abametapir The serum concentration of Alogliptin can be increased when it is combined with Abametapir. Abatacept The metabolism of Alogliptin can be increased when combined with Abatacept. Abiraterone The metabolism of Alogliptin can be decreased when combined with Abiraterone. Acarbose The risk or severity of hypoglycemia can be increased when Acarbose is combined with Alogliptin. - Food Interactions
- Take with or without food.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Product Ingredients
Ingredient UNII CAS InChI Key Alogliptin benzoate EEN99869SC 850649-62-6 KEJICOXJTRHYAK-XFULWGLBSA-N - Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Nesina Tablet 6.25 mg Oral Takeda 2014-04-30 Not applicable Canada 
Nesina Tablet, film coated 6.25 mg/1 Oral Takeda Pharmaceuticals America, Inc. 2013-01-25 Not applicable US 
Nesina Tablet 25 mg Oral Takeda 2014-05-13 Not applicable Canada Nesina Tablet, film coated 25 mg/1 Oral Takeda Pharmaceuticals America, Inc. 2013-01-25 Not applicable US Nesina Tablet 12.5 mg Oral Takeda 2014-04-30 Not applicable Canada - Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Alogliptin Tablet, film coated 25 mg/1 Oral REMEDYREPACK INC. 2024-01-06 Not applicable US Alogliptin Tablet, film coated 25 mg/1 Oral Padagis Israel Pharmaceuticals Ltd 2016-04-08 Not applicable US Alogliptin Tablet, film coated 25 mg/1 Oral Aphena Pharma Solutions - Tennessee, LLC 2016-04-08 Not applicable US Alogliptin Tablet, film coated 12.5 mg/1 Oral Aphena Pharma Solutions - Tennessee, LLC 2016-04-08 Not applicable US Alogliptin Tablet, film coated 12.5 mg/1 Oral Padagis Israel Pharmaceuticals Ltd 2016-04-08 Not applicable US - Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image Alogliptin and Metformin Hydrochloride Alogliptin benzoate (12.5 mg/1) + Metformin hydrochloride (1000 mg/1) Tablet, film coated Oral Padagis Israel Pharmaceuticals Ltd 2016-04-08 Not applicable US Alogliptin and Metformin Hydrochloride Alogliptin benzoate (12.5 mg/1) + Metformin hydrochloride (500 mg/1) Tablet, film coated Oral Padagis Israel Pharmaceuticals Ltd 2016-04-08 Not applicable US Alogliptin and Metformin Hydrochloride Alogliptin benzoate (12.5 mg/1) + Metformin hydrochloride (1000 mg/1) Tablet, film coated Oral A-S Medication Solutions 2016-04-08 Not applicable US Alogliptin and Pioglitazone Alogliptin benzoate (25 mg/1) + Pioglitazone hydrochloride (30 mg/1) Tablet, film coated Oral Padagis Israel Pharmaceuticals Ltd 2016-04-08 Not applicable US Alogliptin and Pioglitazone Alogliptin benzoate (12.5 mg/1) + Pioglitazone hydrochloride (45 mg/1) Tablet, film coated Oral Padagis Israel Pharmaceuticals Ltd 2016-04-08 Not applicable US
Categories
- ATC Codes
- A10BD13 — Metformin and alogliptin
- A10BD — Combinations of oral blood glucose lowering drugs
- A10B — BLOOD GLUCOSE LOWERING DRUGS, EXCL. INSULINS
- A10 — DRUGS USED IN DIABETES
- A — ALIMENTARY TRACT AND METABOLISM
- A10BD — Combinations of oral blood glucose lowering drugs
- A10B — BLOOD GLUCOSE LOWERING DRUGS, EXCL. INSULINS
- A10 — DRUGS USED IN DIABETES
- A — ALIMENTARY TRACT AND METABOLISM
- Drug Categories
- Agents causing angioedema
- Alimentary Tract and Metabolism
- Blood Glucose Lowering Agents
- Cytochrome P-450 CYP2D6 Substrates
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 Substrates
- DPP-IV Inhibitors
- Drugs that are Mainly Renally Excreted
- Drugs Used in Diabetes
- Enzyme Inhibitors
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Incretins
- Oral Hypoglycemics
- Protease Inhibitors
- Pyrimidines
- Pyrimidinones
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as benzonitriles. These are organic compounds containing a benzene bearing a nitrile substituent.
- Kingdom
- Organic compounds
- Super Class
- Benzenoids
- Class
- Benzene and substituted derivatives
- Sub Class
- Benzonitriles
- Direct Parent
- Benzonitriles
- Alternative Parents
- Dialkylarylamines / Pyrimidones / Aminopiperidines / Aminopyrimidines and derivatives / Hydropyrimidines / Vinylogous amides / Heteroaromatic compounds / Ureas / Lactams / Azacyclic compounds show 6 more
- Substituents
- 3-aminopiperidine / Amine / Aminopyrimidine / Aromatic heteromonocyclic compound / Azacycle / Benzonitrile / Carbonitrile / Dialkylarylamine / Heteroaromatic compound / Hydrocarbon derivative show 17 more
- Molecular Framework
- Aromatic heteromonocyclic compounds
- External Descriptors
- piperidines, pyrimidines, primary amino compound, nitrile (CHEBI:72323)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- JHC049LO86
- CAS number
- 850649-61-5
- InChI Key
- ZSBOMTDTBDDKMP-OAHLLOKOSA-N
- InChI
- InChI=1S/C18H21N5O2/c1-21-17(24)9-16(22-8-4-7-15(20)12-22)23(18(21)25)11-14-6-3-2-5-13(14)10-19/h2-3,5-6,9,15H,4,7-8,11-12,20H2,1H3/t15-/m1/s1
- IUPAC Name
- 2-({6-[(3R)-3-aminopiperidin-1-yl]-3-methyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-1-yl}methyl)benzonitrile
- SMILES
- CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O
References
- Synthesis Reference
Kenji Nakamura, Kenichiro Kiyoshima, Junya Nomura, "SOLID PREPARATION COMPRISING ALOGLIPTIN AND PIOGLITAZONE." U.S. Patent US20100092551, issued April 15, 2010.
US20100092551- General References
- Christopher R, Covington P, Davenport M, Fleck P, Mekki QA, Wann ER, Karim A: Pharmacokinetics, pharmacodynamics, and tolerability of single increasing doses of the dipeptidyl peptidase-4 inhibitor alogliptin in healthy male subjects. Clin Ther. 2008 Mar;30(3):513-27. doi: 10.1016/j.clinthera.2008.03.005. [Article]
- Covington P, Christopher R, Davenport M, Fleck P, Mekki QA, Wann ER, Karim A: Pharmacokinetic, pharmacodynamic, and tolerability profiles of the dipeptidyl peptidase-4 inhibitor alogliptin: a randomized, double-blind, placebo-controlled, multiple-dose study in adult patients with type 2 diabetes. Clin Ther. 2008 Mar;30(3):499-512. doi: 10.1016/j.clinthera.2008.03.004. [Article]
- 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. [Article]
- External Links
- KEGG Drug
- D06553
- PubChem Compound
- 11450633
- PubChem Substance
- 175427056
- ChemSpider
- 9625485
- BindingDB
- 16285
- 1368001
- ChEBI
- 72323
- ChEMBL
- CHEMBL376359
- ZINC
- ZINC000014961096
- PDBe Ligand
- T22
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Alogliptin
- PDB Entries
- 3g0b
- FDA label
- Download (648 KB)
- MSDS
- Download (479 KB)
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 4 Active Not Recruiting Treatment Type 2 Diabetes Mellitus 1 4 Completed Treatment Diabetes Mellitus 1 4 Completed Treatment Polycystic Ovarian Syndrome (PCOS) / Resistance, Insulin 1 4 Completed Treatment Type 2 Diabetes Mellitus 4 4 Terminated Treatment Type 2 Diabetes Mellitus 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Tablet Oral 8.500 mg Tablet, coated Oral Tablet Oral Tablet, film coated Oral Tablet Oral 12.5 mg Tablet Oral 25 mg Tablet Oral 6.25 mg Tablet, film coated Oral Tablet, film coated Oral 12.5 mg/1 Tablet, film coated Oral 25 mg/1 Tablet, film coated Oral 6.25 mg/1 Tablet, film coated Oral 12.5 mg Tablet, film coated Oral 12.5 MG Tablet, film coated Oral 25 MG Tablet, film coated Oral 6.25 MG Tablet, coated Oral 12.5 mg Tablet, film coated Oral 25 mg Tablet, coated Oral 25 mg - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US6150383 No 2000-11-21 2016-06-19 US US6211205 No 2001-04-03 2016-06-19 US US6303640 No 2001-10-16 2016-08-09 US US6329404 No 2001-12-11 2016-06-19 US US5965584 No 1999-10-12 2016-06-19 US US6166042 No 2000-12-26 2016-06-19 US US6166043 No 2000-12-26 2016-06-19 US US6172090 No 2001-01-09 2016-06-19 US US6150384 No 2000-11-21 2016-06-19 US US6271243 No 2001-08-07 2016-06-19 US US6303661 No 2001-10-16 2017-04-24 US US6890898 No 2005-05-10 2019-02-02 US US7078381 No 2006-07-18 2019-02-02 US US7459428 No 2008-12-02 2019-02-02 US US7807689 No 2010-10-05 2028-06-27 US US8173663 No 2012-05-08 2025-03-15 US US8288539 No 2012-10-16 2025-03-15 US US8697125 No 2014-04-15 2029-01-22 US US8637079 No 2014-01-28 2029-06-04 US US8900638 No 2014-12-02 2029-05-24 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source water solubility Sparingly soluble FDA label - Predicted Properties
Property Value Source Water Solubility 0.58 mg/mL ALOGPS logP 0.66 ALOGPS logP 1.16 Chemaxon logS -2.8 ALOGPS pKa (Strongest Basic) 9.47 Chemaxon Physiological Charge 1 Chemaxon Hydrogen Acceptor Count 5 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 93.67 Å2 Chemaxon Rotatable Bond Count 3 Chemaxon Refractivity 104.26 m3·mol-1 Chemaxon Polarizability 35.64 Å3 Chemaxon Number of Rings 3 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.9942 Blood Brain Barrier + 0.9738 Caco-2 permeable - 0.5492 P-glycoprotein substrate Substrate 0.6453 P-glycoprotein inhibitor I Non-inhibitor 0.6811 P-glycoprotein inhibitor II Non-inhibitor 0.9238 Renal organic cation transporter Non-inhibitor 0.591 CYP450 2C9 substrate Non-substrate 0.8003 CYP450 2D6 substrate Non-substrate 0.7259 CYP450 3A4 substrate Substrate 0.5528 CYP450 1A2 substrate Non-inhibitor 0.9169 CYP450 2C9 inhibitor Non-inhibitor 0.8475 CYP450 2D6 inhibitor Non-inhibitor 0.9038 CYP450 2C19 inhibitor Non-inhibitor 0.8527 CYP450 3A4 inhibitor Non-inhibitor 0.7608 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9363 Ames test Non AMES toxic 0.5595 Carcinogenicity Non-carcinogens 0.8887 Biodegradation Not ready biodegradable 0.9931 Rat acute toxicity 2.5603 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.5507 hERG inhibition (predictor II) Inhibitor 0.8389
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-0006-0009000000-b5c5f94cc839f451b69b Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-000i-0029000000-48f483b2435f3c867cd9 Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-0006-0019000000-f92369c484f34d437f26 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-0079-0097000000-bdccfdbe30c695befcac Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-059y-5693000000-ec84fbf390d84c0a3e32 Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-0159-0491000000-57fc6770a9441a66ad54 Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 193.9398697 predictedDarkChem Lite v0.1.0 [M-H]- 175.75768 predictedDeepCCS 1.0 (2019) [M+H]+ 195.0411697 predictedDarkChem Lite v0.1.0 [M+H]+ 178.11568 predictedDeepCCS 1.0 (2019) [M+Na]+ 194.2153697 predictedDarkChem Lite v0.1.0 [M+Na]+ 185.73883 predictedDeepCCS 1.0 (2019)
Targets
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Use our structured and evidence-based datasets to unlock newinsights and accelerate drug research.
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- Kind
- Protein
- Organism
- Humans
- 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 bindi...
- Gene Name
- DPP4
- Uniprot ID
- P27487
- Uniprot Name
- Dipeptidyl peptidase 4
- Molecular Weight
- 88277.935 Da
References
- Nadkarni P, Chepurny OG, Holz GG: Regulation of glucose homeostasis by GLP-1. Prog Mol Biol Transl Sci. 2014;121:23-65. doi: 10.1016/B978-0-12-800101-1.00002-8. [Article]
- Gallwitz B: Novel Therapeutic Approaches in Diabetes. Endocr Dev. 2016;31:43-56. doi: 10.1159/000439372. Epub 2016 Jan 19. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- 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
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- 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
Drug created at March 19, 2008 16:17 / Updated at February 20, 2024 23:55