Identification

Name
Pioglitazone
Accession Number
DB01132
Description

Pioglitazone is an antihyperglycemic used as an adjunct to diet, exercise, and other antidiabetic medications to manage type 2 diabetes mellitus.4,5,6,7 It is administered as a racemic mixture, though there is no pharmacologic difference between the enantiomers and they appear to interconvert in vivo with little consequence.4 The thiazolidinedione class of medications, which also includes rosiglitazone and troglitazone, exerts its pharmacological effect primarily by promoting insulin sensitivity and the improved uptake of blood glucose4 via agonism at the peroxisome proliferator-activated receptor-gamma (PPARγ).1 PPARs are ligand-activated transcription factors that are involved in the expression of more than 100 genes and affect numerous metabolic processes, most notably lipid and glucose homeostasis.2

Thiazolidinediones, including pioglitazone, have fallen out of favor in recent years due to the presence of multiple adverse effects and warnings regarding their use (e.g. congestive heart failure, bladder cancer) and the availability of safer and more effective alternatives for patients with type 2 diabetes mellitus.9

Type
Small Molecule
Groups
Approved, Investigational
Structure
Thumb
Weight
Average: 356.439
Monoisotopic: 356.119463206
Chemical Formula
C19H20N2O3S
Synonyms
  • (±)-5-((4-(2-(5-ethyl-2-pyridinyl)ethoxy)phenyl)methyl)-2,4-thiazolidinedione
  • 5-{4-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl}-1,3-thiazolidine-2,4-dione
  • Pioglitazona
  • Pioglitazone
  • Pioglitazonum
External IDs
  • AD-4833
  • U 72107A
  • U-72107A
  • U72107A

Pharmacology

Indication

Pioglitazone is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.4 It is also available in combination with metformin,5 glimepiride,6 or alogliptin7 for the same indication.

Associated Conditions
Contraindications & Blackbox Warnings
Learn about our commercial Contraindications & Blackbox Warnings data.
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Pharmacodynamics

Pioglitazone enhances cellular responsiveness to insulin, increases insulin-dependent glucose disposal, and improves impaired glucose homeostasis.1 In patients with type 2 diabetes mellitus, these effects result in lower plasma glucose concentrations, lower plasma insulin concentrations, and lower HbA1c values.1

Significant fluid retention leading to the development/exacerbation of congestive heart failure has been reported with pioglitazone - avoid its use in patients in heart failure or at risk of developing heart failure.4 There is some evidence that pioglitazone may be associated with an increased risk of developing bladder cancer. Pioglitazone should not be used in patients with active bladder cancer and should be used with caution in patients with a history of bladder cancer.4

Mechanism of action

Pioglitazone is a selective agonist at peroxisome proliferator-activated receptor-gamma (PPARγ) in target tissues for insulin action such as adipose tissue, skeletal muscle, and liver.4,2 Activation of PPARγ increases the transcription of insulin-responsive genes involved in the control of glucose and lipid production, transport, and utilization.2 Through this mechanism, pioglitazone both enhances tissue sensitivity to insulin and reduces the hepatic production of glucose (i.e. gluconeogenesis) - insulin resistance associated with type 2 diabetes mellitus is therefore improved without an increase in insulin secretion by pancreatic beta cells.4,2

TargetActionsOrganism
APeroxisome proliferator-activated receptor gamma
agonist
Humans
UAmine oxidase [flavin-containing] B
inhibitor
Humans
Absorption

Following oral administration of pioglitazone, peak serum concentrations are observed within 2 hours (Tmax) - food slightly delays the time to peak serum concentration, increasing Tmax to approximately 3-4 hours, but does not alter the extent of absorption.4 Steady-state concentrations of both parent drug and its primary active metabolites are achieved after 7 days of once-daily administration of pioglitazone.4 Cmax and AUC increase proportionately to administered doses.4

Volume of distribution

The average apparent volume of distribution of pioglitazone is 0.63 ± 0.41 L/kg.4

Protein binding

Pioglitazone is >99% protein-bound in human plasma - binding is primarily to albumin, although pioglitazone has been shown to bind other serum proteins with a lower affinity.4 The M-III and M-IV metabolites of pioglitazone are >98% protein-bound (also primarily to albumin).4

Metabolism

Pioglitazone is extensively metabolized by both hydroxylation and oxidation - the resulting metabolites are also partly converted to glucuronide or sulfate conjugates.4 The pharmacologically active M-IV and M-III metabolites are the main metabolites found in human serum and their circulating concentrations are equal to, or greater than, those of the parent drug.3 The specific CYP isoenzymes involved in the metabolism of pioglitazone are CYP2C8 and, to a lesser degree, CYP3A4. There is also some evidence to suggest a contribution by extrahepatic CYP1A1.4

Hover over products below to view reaction partners

Route of elimination

Approximately 15-30% of orally administered pioglitazone is recovered in the urine. The bulk of its elimination, then, is presumed to be through the excretion of unchanged drug in the bile or as metabolites in the feces.4

Half-life

The mean serum half-life of pioglitazone and its metabolites (M-III and M-IV) range from 3-7 hours and 16-24 hours, respectively.4

Clearance

The apparent clearance of orally administered pioglitazone is 5-7 L/h.4

Adverse Effects
Learn about our commercial Adverse Effects data.
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Toxicity

The oral TDLo observed in mice is 24 mg/kg for 4 days and for rats is 3 mg/kg for 6 days.8

One instance of overdose was reported during clinical trials with pioglitazone in which a patient took an oral dose of 120mg daily for four days, followed by 180mg daily for seven days4 - this patient did not report any adverse clinical symptoms during this time. In the event of overdosage, employ symptomatic and supportive measures according to the patient's clinical status.4

Affected organisms
  • Humans and other mammals
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
AbametapirThe serum concentration of Pioglitazone can be increased when it is combined with Abametapir.
AbataceptThe metabolism of Pioglitazone can be increased when combined with Abatacept.
AbirateroneThe metabolism of Pioglitazone can be decreased when combined with Abiraterone.
AcarboseThe risk or severity of hypoglycemia can be increased when Acarbose is combined with Pioglitazone.
AcebutololThe therapeutic efficacy of Pioglitazone can be increased when used in combination with Acebutolol.
AcetazolamideThe therapeutic efficacy of Pioglitazone can be increased when used in combination with Acetazolamide.
AcetohexamideThe therapeutic efficacy of Pioglitazone can be increased when used in combination with Acetohexamide.
Acetyl sulfisoxazoleThe therapeutic efficacy of Pioglitazone can be increased when used in combination with Acetyl sulfisoxazole.
Acetylsalicylic acidThe risk or severity of hypoglycemia can be increased when Acetylsalicylic acid is combined with Pioglitazone.
AdalimumabThe metabolism of Pioglitazone can be increased when combined with Adalimumab.
Additional Data Available
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  • Severity
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  • Evidence Level
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  • Action
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Food Interactions
  • Take with or without food. Food delays drug absorption, but not to a clinically significant extent.

Products

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Product Ingredients
IngredientUNIICASInChI Key
Pioglitazone hydrochlorideJQT35NPK6C112529-15-4GHUUBYQTCDQWRA-UHFFFAOYSA-N
Product Images
International/Other Brands
Actost
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Act PioglitazoneTabletOralTEVA Canada Limited2007-12-05Not applicableCanada flag
Act PioglitazoneTabletOralTEVA Canada Limited2007-12-05Not applicableCanada flag
Act PioglitazoneTabletOralTEVA Canada Limited2007-12-05Not applicableCanada flag
ActosTablet30 mg/1OralCardinal Health1999-07-152013-05-31US flag
ActosTablet30 mg/1OralRebel Distributors1999-07-15Not applicableUS flag
ActosTablet30 mgOralTakeda Pharma A/S2000-10-13Not applicableEU flag
ActosTablet15 mgOralTakeda Pharma A/S2000-10-13Not applicableEU flag
ActosTablet30 mgOralTakeda Pharma A/S2000-10-13Not applicableEU flag
ActosTablet45 mg/1OralPhysicians Total Care, Inc.2009-10-22Not applicableUS flag
ActosTablet45 mgOralTakeda2000-08-282018-03-30Canada flag
Additional Data Available
  • Application Number
    Application Number
    Available for Purchase

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code
    Available for Purchase

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Accel PioglitazoneTabletOralAccel Pharma Inc2009-06-022020-03-20Canada flag
Accel PioglitazoneTabletOralAccel Pharma Inc2009-06-022020-03-20Canada flag
Accel PioglitazoneTabletOralAccel Pharma Inc2009-06-022020-03-20Canada flag
Ach-pioglitazoneTabletOralAccord Healthcare Inc2012-10-12Not applicableCanada flag
Ach-pioglitazoneTabletOralAccord Healthcare Inc2010-06-11Not applicableCanada flag
Ach-pioglitazoneTabletOralAccord Healthcare Inc2010-06-11Not applicableCanada flag
Ag-pioglitazoneTabletOralAngita Pharma Inc.Not applicableNot applicableCanada flag
Ag-pioglitazoneTabletOralAngita Pharma Inc.Not applicableNot applicableCanada flag
Apo-pioglitazoneTabletOralApotex Corporation2007-12-05Not applicableCanada flag
Apo-pioglitazoneTabletOralApotex Corporation2007-12-05Not applicableCanada flag
Additional Data Available
  • Application Number
    Application Number
    Available for Purchase

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code
    Available for Purchase

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
Actoplus MetPioglitazone hydrochloride (15 mg/1) + Metformin hydrochloride (850 mg/1)Tablet, film coatedOralTakeda Pharmaceuticals America, Inc.2005-08-29Not applicableUS flag
Actoplus MetPioglitazone hydrochloride (15 mg/1) + Metformin hydrochloride (500 mg/1)Tablet, film coatedOralPhysicians Total Care, Inc.2006-01-04Not applicableUS flag
Actoplus MetPioglitazone hydrochloride (15 mg/1) + Metformin hydrochloride (500 mg/1)Tablet, film coatedOralTakeda Pharmaceuticals America, Inc.2005-08-29Not applicableUS flag
Actoplus MetPioglitazone hydrochloride (15 mg/1) + Metformin hydrochloride (850 mg/1)Tablet, film coatedOralCardinal Health2005-08-292014-05-31US flag
Actoplus MetPioglitazone hydrochloride (15 mg/1) + Metformin hydrochloride (850 mg/1)Tablet, film coatedOralPhysicians Total Care, Inc.2006-03-21Not applicableUS flag
Actoplus Met XRPioglitazone hydrochloride (30 mg/1) + Metformin hydrochloride (1000 mg/1)Tablet, film coated, extended releaseOralTakeda Pharmaceuticals America, Inc.2010-06-112022-09-30US flag
Actoplus Met XRPioglitazone hydrochloride (15 mg/1) + Metformin hydrochloride (1000 mg/1)Tablet, film coated, extended releaseOralTakeda Pharmaceuticals America, Inc.2010-06-112022-09-30US flag
Alogliptin and PioglitazonePioglitazone hydrochloride (30 mg/1) + Alogliptin benzoate (25 mg/1)Tablet, film coatedOralPerrigo New York Inc2016-04-08Not applicableUS flag
Alogliptin and PioglitazonePioglitazone hydrochloride (45 mg/1) + Alogliptin benzoate (12.5 mg/1)Tablet, film coatedOralPerrigo New York Inc2016-04-08Not applicableUS flag
Alogliptin and PioglitazonePioglitazone hydrochloride (45 mg/1) + Alogliptin benzoate (25 mg/1)Tablet, film coatedOralPerrigo New York Inc2016-04-08Not applicableUS flag

Categories

ATC Codes
A10BD09 — Pioglitazone and alogliptinA10BG03 — PioglitazoneA10BD05 — Metformin and pioglitazoneA10BD06 — Glimepiride and pioglitazoneA10BD12 — Pioglitazone and sitagliptin
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as phenol ethers. These are aromatic compounds containing an ether group substituted with a benzene ring.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Phenol ethers
Sub Class
Not Available
Direct Parent
Phenol ethers
Alternative Parents
Phenoxy compounds / Thiazolidinediones / Alkyl aryl ethers / Pyridines and derivatives / Heteroaromatic compounds / Dicarboximides / Thiocarbamic acid derivatives / Organic carbonic acids and derivatives / Azacyclic compounds / Organopnictogen compounds
show 4 more
Substituents
Alkyl aryl ether / Aromatic heteromonocyclic compound / Azacycle / Carbonic acid derivative / Carbonyl group / Carboxylic acid derivative / Dicarboximide / Ether / Heteroaromatic compound / Hydrocarbon derivative
show 14 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
aromatic ether, pyridines, thiazolidenediones (CHEBI:8228)

Chemical Identifiers

UNII
X4OV71U42S
CAS number
111025-46-8
InChI Key
HYAFETHFCAUJAY-UHFFFAOYSA-N
InChI
InChI=1S/C19H20N2O3S/c1-2-13-3-6-15(20-12-13)9-10-24-16-7-4-14(5-8-16)11-17-18(22)21-19(23)25-17/h3-8,12,17H,2,9-11H2,1H3,(H,21,22,23)
IUPAC Name
5-({4-[2-(5-ethylpyridin-2-yl)ethoxy]phenyl}methyl)-1,3-thiazolidine-2,4-dione
SMILES
CCC1=CN=C(CCOC2=CC=C(CC3SC(=O)NC3=O)C=C2)C=C1

References

Synthesis Reference

Chandra Khanduri, Yatendra Kumar, Atulya Panda, Suchitra Chakraborty, Mukesh Sharma, "Process for the preparation of pioglitazone." U.S. Patent US20070078170, issued April 05, 2007.

US20070078170
General References
  1. Al-Majed A, Bakheit AH, Abdel Aziz HA, Alharbi H, Al-Jenoobi FI: Pioglitazone. Profiles Drug Subst Excip Relat Methodol. 2016;41:379-438. doi: 10.1016/bs.podrm.2015.11.002. Epub 2016 Feb 2. [PubMed:26940171]
  2. Janani C, Ranjitha Kumari BD: PPAR gamma gene--a review. Diabetes Metab Syndr. 2015 Jan-Mar;9(1):46-50. doi: 10.1016/j.dsx.2014.09.015. Epub 2014 Oct 13. [PubMed:25450819]
  3. Zhou SF, Zhou ZW, Yang LP, Cai JP: 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. Epub 2009 Sep 1. [PubMed:19515014]
  4. FDA Approved Drug Products: Actos (pioglitazone) oral tablets [Link]
  5. FDA Approved Drug Products: Actoplus Met (pioglitazone/metformin) oral tablets [Link]
  6. FDA Approved Drug Products: Duetact (pioglitazone/glimepiride) oral tablets [Link]
  7. FDA Approved Drug Products: Oseni (pioglitazone/alogliptin) oral tablets [Link]
  8. CaymanChem: Pioglitazone MSDS [Link]
  9. Diabetes Canada: Clinical Practice Guidelines for Diabetes 2018 [Link]
Human Metabolome Database
HMDB0015264
KEGG Drug
D08378
KEGG Compound
C07675
PubChem Compound
4829
PubChem Substance
46507136
ChemSpider
4663
BindingDB
50103521
RxNav
33738
ChEBI
8228
ChEMBL
CHEMBL595
Therapeutic Targets Database
DAP000272
PharmGKB
PA450970
Guide to Pharmacology
GtP Drug Page
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Pioglitazone
AHFS Codes
  • 68:20.28 — Thiazolidinediones
FDA label
Download (61.6 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4Active Not RecruitingBasic ScienceUric Acid Nephrolithiasis1
4Active Not RecruitingTreatmentDiabetes1
4Active Not RecruitingTreatmentType 2 Diabetes Mellitus2
4CompletedNot AvailableType 2 Diabetes Mellitus1
4CompletedBasic ScienceDiabetes1
4CompletedBasic ScienceDiabetes / Glucose Metabolism Disorders1
4CompletedBasic ScienceInsulin Resistance / Metabolic Syndromes / Pre-Diabetic1
4CompletedBasic ScienceType 2 Diabetes Mellitus2
4CompletedPreventionAdverse Effects / Coronary Artery Atherosclerosis / Insulin resistance syndrome1
4CompletedPreventionAngina Pectoris / Coronary Artery Disease (CAD) / Percutaneous Coronary Intervention (PCI) / Type 2 Diabetes Mellitus1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Advanced Pharmaceutical Services Inc.
  • AQ Pharmaceuticals Inc.
  • A-S Medication Solutions LLC
  • Atlantic Biologicals Corporation
  • Cardinal Health
  • Comprehensive Consultant Services Inc.
  • DispenseXpress Inc.
  • Diversified Healthcare Services Inc.
  • Kaiser Foundation Hospital
  • Lake Erie Medical and Surgical Supply
  • Murfreesboro Pharmaceutical Nursing Supply
  • Nucare Pharmaceuticals Inc.
  • Palmetto Pharmaceuticals Inc.
  • PD-Rx Pharmaceuticals Inc.
  • Pharmacy Service Center
  • Physician Partners Ltd.
  • Physicians Total Care Inc.
  • Prepackage Specialists
  • Quality Care
  • Rebel Distributors Corp.
  • Resource Optimization and Innovation LLC
  • Southwood Pharmaceuticals
  • Takeda Pharmaceutical Co. Ltd.
  • Vangard Labs Inc.
Dosage Forms
FormRouteStrength
Tablet, film coatedOral15 mg
Tablet, film coated, extended releaseOral
TabletOcclusive dressing technique15 mg/1
TabletOral15 mg/1
TabletOral30 mg/1
TabletOral45 mg/1
Tablet15 mg
Tablet30 mg
Tablet
Tablet, effervescent15 mg
Tablet, effervescent30 mg
Tablet, effervescent45 mg
Tablet45 mg
Tablet, coatedOral500 mg
Tablet, coatedOral850 mg
TabletOral15 mg
TabletOral30 mg
TabletOral45 mg
Tablet, coatedOral15 mg
Tablet, extended releaseOral15 mg
Tablet, effervescentOral15 mg
Tablet, effervescentOral30 mg
Tablet, coatedOral12.5 MG
Tablet, film coatedOral
Tablet, coatedOral25 mg
Tablet, coatedOral30 mg
Tablet, coatedOral45 mg
Tablet, film coated15 mg
Tablet, film coated30 mg
Tablet, film coated45 mg
Tablet, film coatedOral850 mg
TabletOral
TabletOral
Prices
Unit descriptionCostUnit
Actos 30 mg tablet12.48USD tablet
Actos 45 mg tablet11.22USD tablet
Actos 15 mg tablet6.3USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US4687777No1987-08-182011-01-17US flag
CA2179584No2007-04-242016-06-20Canada flag
CA2531834No2006-12-052016-06-20Canada flag
US6150383No2000-11-212016-06-19US flag
US6211205No2001-04-032016-06-19US flag
US6303640No2001-10-162016-08-09US flag
US6329404No2001-12-112016-06-19US flag
US8071130No2011-12-062028-06-08US flag
US7538125No2009-05-262016-06-19US flag
US7700128No2010-04-202027-01-30US flag
US5965584No1999-10-122016-06-19US flag
US6166042No2000-12-262016-06-19US flag
US6166043No2000-12-262016-06-19US flag
US6172090No2001-01-092016-06-19US flag
US6790459No2004-09-142021-03-17US flag
US7919116No2011-04-052018-03-20US flag
US8475841No2013-07-022018-03-20US flag
US6099859No2000-08-082018-03-20US flag
US6866866No2005-03-152021-03-17US flag
US7785627No2010-08-312026-07-31US flag
US7959946No2011-06-142026-07-31US flag
US8470368No2013-06-252023-09-19US flag
US8668931No2014-03-112023-09-19US flag
US9060941No2015-06-232023-09-19US flag
US6495162No2002-12-172018-03-20US flag
US6150384No2000-11-212016-06-19US flag
US6271243No2001-08-072016-06-19US flag
US9101660No2015-08-112027-01-22US flag
US6303661No2001-10-162017-04-24US flag
US6890898No2005-05-102019-02-02US flag
US7078381No2006-07-182019-02-02US flag
US7459428No2008-12-022019-02-02US flag
US7807689No2010-10-052028-06-27US flag
US8173663No2012-05-082025-03-15US flag
US8288539No2012-10-162025-03-15US flag
US8637079No2014-01-282029-06-04US flag
US9320714No2016-04-262029-02-03US flag
Additional Data Available
  • Filed On
    Filed On
    Available for Purchase

    The date on which a patent was filed with the relevant government.

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Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)193-194CAl-Majed, A. et. al.
water solubilityPractically insolubleFDA Label
pKa5.19Al-Majed, A. et. al.
Predicted Properties
PropertyValueSource
Water Solubility0.00442 mg/mLALOGPS
logP3.17ALOGPS
logP3.33ChemAxon
logS-4.9ALOGPS
pKa (Strongest Acidic)6.66ChemAxon
pKa (Strongest Basic)5.6ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area68.29 Å2ChemAxon
Rotatable Bond Count7ChemAxon
Refractivity97.39 m3·mol-1ChemAxon
Polarizability37.91 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.9952
Blood Brain Barrier+0.8753
Caco-2 permeable-0.5659
P-glycoprotein substrateNon-substrate0.6358
P-glycoprotein inhibitor INon-inhibitor0.5708
P-glycoprotein inhibitor IINon-inhibitor0.9673
Renal organic cation transporterNon-inhibitor0.6018
CYP450 2C9 substrateNon-substrate0.7898
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateSubstrate0.5267
CYP450 1A2 substrateInhibitor0.8384
CYP450 2C9 inhibitorInhibitor0.6353
CYP450 2D6 inhibitorNon-inhibitor0.8085
CYP450 2C19 inhibitorInhibitor0.6967
CYP450 3A4 inhibitorNon-inhibitor0.6035
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.8864
Ames testNon AMES toxic0.7303
CarcinogenicityNon-carcinogens0.9171
BiodegradationNot ready biodegradable0.7884
Rat acute toxicity2.0115 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9341
hERG inhibition (predictor II)Non-inhibitor0.8498
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0a4i-0009000000-070cf69939743719671d
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0bt9-0209000000-d9d34be41f49a9ffbdef
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0udi-0900000000-ef25b6f93ae4fcee23c3
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0udi-0900000000-3011f00e839bfc06d89d
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0gba-0900000000-b0488e0d155d1587bbb5
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-014j-0900000000-b32570ad6af58a4a6c72
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0a4i-0009000000-c67370f6cb2ad36cab3e
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0a59-0908000000-aab2ee9addb1334a7064
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0a4i-0009000000-fd4bc4d9d4bb45e91295
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0a4i-0409000000-115c6889c4e9205b3028
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-001i-0900000000-a2e878da4d2f6a4bb717
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-001i-0900000000-031fa259cd3b26217dad
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-00lr-0900000000-e2cd3c294a2e53e1a17e
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0159-1900000000-aacbd8dce006b5ef5938
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0a4i-1619000000-4b248e31af7f50e87108
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-053r-0906000000-a73152b364036b45dfeb

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Agonist
General Function
Zinc ion binding
Specific Function
Nuclear receptor that binds peroxisome proliferators such as hypolipidemic drugs and fatty acids. Once activated by a ligand, the nuclear receptor binds to DNA specific PPAR response elements (PPRE...
Gene Name
PPARG
Uniprot ID
P37231
Uniprot Name
Peroxisome proliferator-activated receptor gamma
Molecular Weight
57619.58 Da
References
  1. Sugii S, Olson P, Sears DD, Saberi M, Atkins AR, Barish GD, Hong SH, Castro GL, Yin YQ, Nelson MC, Hsiao G, Greaves DR, Downes M, Yu RT, Olefsky JM, Evans RM: PPARgamma activation in adipocytes is sufficient for systemic insulin sensitization. Proc Natl Acad Sci U S A. 2009 Dec 29;106(52):22504-9. doi: 10.1073/pnas.0912487106. Epub 2009 Dec 16. [PubMed:20018750]
  2. Miyazaki Y, Mahankali A, Wajcberg E, Bajaj M, Mandarino LJ, DeFronzo RA: Effect of pioglitazone on circulating adipocytokine levels and insulin sensitivity in type 2 diabetic patients. J Clin Endocrinol Metab. 2004 Sep;89(9):4312-9. [PubMed:15356026]
  3. Spiegelman BM: PPAR-gamma: adipogenic regulator and thiazolidinedione receptor. Diabetes. 1998 Apr;47(4):507-14. [PubMed:9568680]
  4. Willson TM, Cobb JE, Cowan DJ, Wiethe RW, Correa ID, Prakash SR, Beck KD, Moore LB, Kliewer SA, Lehmann JM: The structure-activity relationship between peroxisome proliferator-activated receptor gamma agonism and the antihyperglycemic activity of thiazolidinediones. J Med Chem. 1996 Feb 2;39(3):665-8. [PubMed:8576907]
  5. FDA Approved Drug Products: Actos (pioglitazone) oral tablets [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Primary amine oxidase activity
Specific Function
Catalyzes the oxidative deamination of biogenic and xenobiotic amines and has important functions in the metabolism of neuroactive and vasoactive amines in the central nervous system and peripheral...
Gene Name
MAOB
Uniprot ID
P27338
Uniprot Name
Amine oxidase [flavin-containing] B
Molecular Weight
58762.475 Da
References
  1. Binda C, Aldeco M, Geldenhuys WJ, Tortorici M, Mattevi A, Edmondson DE: Molecular Insights into Human Monoamine Oxidase B Inhibition by the Glitazone Anti-Diabetes Drugs. ACS Med Chem Lett. 2011 Oct 15;3(1):39-42. [PubMed:22282722]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
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
CYP2C8
Uniprot ID
P10632
Uniprot Name
Cytochrome P450 2C8
Molecular Weight
55824.275 Da
References
  1. Muschler E, Lal J, Jetter A, Rattay A, Zanger U, Zadoyan G, Fuhr U, Kirchheiner J: The role of human CYP2C8 and CYP2C9 variants in pioglitazone metabolism in vitro. Basic Clin Pharmacol Toxicol. 2009 Dec;105(6):374-9. doi: 10.1111/j.1742-7843.2009.00457.x. Epub 2009 Jul 15. [PubMed:19614891]
  2. Jaakkola T, Laitila J, Neuvonen PJ, Backman JT: Pioglitazone is metabolised by CYP2C8 and CYP3A4 in vitro: potential for interactions with CYP2C8 inhibitors. Basic Clin Pharmacol Toxicol. 2006 Jul;99(1):44-51. doi: 10.1111/j.1742-7843.2006.pto_437.x. [PubMed:16867170]
  3. Sahi J, Black CB, Hamilton GA, Zheng X, Jolley S, Rose KA, Gilbert D, LeCluyse EL, Sinz MW: Comparative effects of thiazolidinediones on in vitro P450 enzyme induction and inhibition. Drug Metab Dispos. 2003 Apr;31(4):439-46. [PubMed:12642470]
  4. Zhou SF, Zhou ZW, Yang LP, Cai JP: 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. Epub 2009 Sep 1. [PubMed:19515014]
  5. FDA Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inducer
Curator comments
One study suggests that another thiazolidinedione, troglitazone, induces CYP3A4. Pioglitazone is a member of the same drug class, and likely has the same effect.
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. Jaakkola T, Laitila J, Neuvonen PJ, Backman JT: Pioglitazone is metabolised by CYP2C8 and CYP3A4 in vitro: potential for interactions with CYP2C8 inhibitors. Basic Clin Pharmacol Toxicol. 2006 Jul;99(1):44-51. doi: 10.1111/j.1742-7843.2006.pto_437.x. [PubMed:16867170]
  2. Sahi J, Black CB, Hamilton GA, Zheng X, Jolley S, Rose KA, Gilbert D, LeCluyse EL, Sinz MW: Comparative effects of thiazolidinediones on in vitro P450 enzyme induction and inhibition. Drug Metab Dispos. 2003 Apr;31(4):439-46. [PubMed:12642470]
  3. Nowak SN, Edwards DJ, Clarke A, Anderson GD, Jaber LA: Pioglitazone: effect on CYP3A4 activity. J Clin Pharmacol. 2002 Dec;42(12):1299-302. [PubMed:12463723]
  4. Zhou SF, Zhou ZW, Yang LP, Cai JP: 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. Epub 2009 Sep 1. [PubMed:19515014]
  5. Flockhart Table of Drug Interactions [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
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. FDA Approved Drug Products: Actos (pioglitazone) oral tablets [Link]

Carriers

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da
References
  1. FDA Approved Drug Products: Actos (pioglitazone) oral tablets [Link]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent uptake of organic anions such as 17-beta-glucuronosyl estradiol, taurocholate, triiodothyronine (T3), leukotriene C4, dehydroepiandrosterone sulfate (DHEAS), methotre...
Gene Name
SLCO1B3
Uniprot ID
Q9NPD5
Uniprot Name
Solute carrier organic anion transporter family member 1B3
Molecular Weight
77402.175 Da
References
  1. Nozawa T, Sugiura S, Nakajima M, Goto A, Yokoi T, Nezu J, Tsuji A, Tamai I: Involvement of organic anion transporting polypeptides in the transport of troglitazone sulfate: implications for understanding troglitazone hepatotoxicity. Drug Metab Dispos. 2004 Mar;32(3):291-4. [PubMed:14977862]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent uptake of organic anions such as pravastatin, taurocholate, methotrexate, dehydroepiandrosterone sulfate, 17-beta-glucuronosyl estradiol, estrone sulfate, prostagland...
Gene Name
SLCO1B1
Uniprot ID
Q9Y6L6
Uniprot Name
Solute carrier organic anion transporter family member 1B1
Molecular Weight
76447.99 Da
References
  1. Nozawa T, Sugiura S, Nakajima M, Goto A, Yokoi T, Nezu J, Tsuji A, Tamai I: Involvement of organic anion transporting polypeptides in the transport of troglitazone sulfate: implications for understanding troglitazone hepatotoxicity. Drug Metab Dispos. 2004 Mar;32(3):291-4. [PubMed:14977862]

Drug created on June 13, 2005 07:24 / Updated on November 23, 2020 09:08

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