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Drug

D0098 | Pioglitazone

Molecular Formula C19H20N2O3S
Molecular Weight 356.4
Structure
State solid
Clearance The apparent clearance of orally administered pioglitazone is 5 - 7 L/h [FDA Label].
Volume of distribution 0.63 ± 0.41 L/kg [FDA Label]
Route of elimination Following oral administration, approximately 15% to 30% of the pioglitazone dose is recovered in the urine. Renal elimination of pioglitazone is negligible, and the drug is excreted primarily as metabolites and their conjugates. It is presumed that most of the oral dose is excreted into the bile either unchanged or as metabolites and eliminated in the feces [FDA Label].
Protein binding Pioglitazone is extensively protein bound (> 99%) in human serum, principally to serum albumin. Pioglitazone also binds to other serum proteins, but with lower affinity [FDA Label].
Half life The mean serum half-life of pioglitazone and its metabolites (M-III and M-IV) range from 3 to 7 hours and 16 to 24 hours, respectively [FDA Label].
Absorption Following oral administration of pioglitazone, peak concentrations of pioglitazone were observed within 2 hours. Food slightly delays the time to peak serum concentration (T max) to 3 to 4 hours, but does not alter the extent of absorption (AUC). Steady state concentrations are achieved after 7 days of once daily administration of pioglitazone [FDA Label].
Trade names Actos
Description anti-diabetic thiazolidinediones (TZDs); medication used to treat type 2 diabetes

A

A10BG03 Pioglitazone


[A10BG] Thiazolidinediones


[A10B] BLOOD GLUCOSE LOWERING DRUGS, EXCL. INSULINS


[A10] DRUGS USED IN DIABETES


[A] Alimentary tract and metabolism

A10BD12 Pioglitazone and sitagliptin


[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

A10BD09 Pioglitazone 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

A10BD06 Glimepiride and pioglitazone


[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

A10BD05 Metformin and pioglitazone


[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

Toxicity Dose Time Species Model Method Action Positive criterion Reference
TRANSMEMBRANE POTENTIAL 10–25 μM 3min male CD-1 mice isolated liver mitochondria The electrical transmembrane potential of mitochondria was monitored spectrophotometrically with the cationic dye, rhodamine 123, and monitored at the 505/535 nm. Negative 331
TRANSMEMBRANE POTENTIAL 50 μM 3min male CD-1 mice isolated liver mitochondria The electrical transmembrane potential of mitochondria was monitored spectrophotometrically with the cationic dye, rhodamine 123, and monitored at the 505/535 nm. decrease p < 0.05, significantly different from the control 331
TRANSMEMBRANE POTENTIAL 25-50 µM ZDF fa/fa rat & ZDF lean rat isolated liver mitochondria The transmembrane potential of the mitochondria was monitored spectrophotometrically using rhodamine-123. decrease significantly different from control group (p < 0.05) 225
OPENING OF PERMEABILITY TRANSITION PORE (PTP) 50 μM male CD-1 mice isolated liver mitochondria Mitochondrial swelling as the indicator of mitochondrial permeability transition (MPT) was estimated from the decrease in absorbance at 540 nm. Negative 331
STATE 3 RESPIRATION decrease 22
RESPIRATORY CONTROL RATIO (RCR) 25-50 μM ZDF fa/fa rat & ZDF lean rat isolated liver mitochondria OCR and measured using a fluorescent oxygen probe (Presens) decrease significantly different from control (p < 0.05) 225
RESPIRATORY CONTROL RATIO (RCR) 10-50 μM ZDF fa/fa rat & ZDF lean rat isolated liver mitochondria OCR and measured using a fluorescent oxygen probe (Presens) Negative 225
OXYGEN CONSUMPTION RATE (OCR) 100 μM 2 minutes human HepG2 Measurement of OCR Negative EC50 7
OXYGEN CONSUMPTION RATE (OCR) 100 μM 2 minutes feline cardiomyocytes Measurement of OCR Negative EC50 7
ELECTRON TRANSPORT CHAIN decrease 22
ELECTRON TRANSPORT CHAIN decrease 35
ELECTRON TRANSPORT CHAIN decrease 35
ELECTRON TRANSPORT CHAIN inhibit 197
GLYCOLYSIS 21
ECAR 100 μM 2 minutes human HepG2 Measurement of ECAR Negative EC50 7
ECAR 100 μM 2 minutes feline cardiomyocytes Measurement of ECAR Negative EC50 7
GLUCOSE GALACTOSE IC50 RATIO 300.0 ± 0 ,300.0 ± 0, 1, 300.0 ± 0, 300.0 ± 0, 1 4hr H9c2 cells high-glucose–galactose cell viability assay with JC-1 mitochondrial membrane potential and ATP-depletion assays (CellTiter-Glo reagent ). Negative glucose/galactose IC50 ratio (JC-1 IC50 in glucose, JC-1 IC50 in galactose, JC-1 glu/gla, ATP IC50 in glucose, ATP IC50 in galactose, ATP glu/gla ) 50
ACCUMULATION OF CALCIUM 50 μM male CD-1 mice isolated liver mitochondria Assessment of mitochondrial Ca2+ efflux with arsenazo III at 675/685 nm. Negative 331

Target Dose Time Species Model Method Action Positive criterion Reference
NADH:ubiquinone reductase inhibitor 22
NADH:ubiquinone reductase inhibitor 35
Quinol--cytochrome-c reductase inhibitor 35

Pictogram Signal Statements Precautionary Statement Codes
Warning

Aggregated GHS information provided by 5 companies from 3 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.


H302+H312+H332 (20%): Harmful if swallowed, in contact with skin or if inhaled [Warning Acute toxicity, oral


acute toxicity, dermal


acute toxicity, inhalation]


H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]


H312 (80%): Harmful in contact with skin [Warning Acute toxicity, dermal]


H315 (20%): Causes skin irritation [Warning Skin corrosion/irritation]


H319 (20%): Causes serious eye irritation [Warning Serious eye damage/eye irritation]


H332 (80%): Harmful if inhaled [Warning Acute toxicity, inhalation]


H335 (20%): May cause respiratory irritation [Warning Specific target organ toxicity, single exposure


Respiratory tract irritation]


Information may vary between notifications depending on impurities, additives, and other factors. The percentage value in parenthesis indicates the notified classification ratio from companies that provide hazard codes. Only hazard codes with percentage values above 10% are shown.


 P261, P264, P270, P271, P280, P301+P312, P302+P352, P304+P312, P304+P340, P305+P351+P338, P312, P321, P322, P330, P332+P313, P337+P313, P362, P363, P403+P233, P405, and P501; (The corresponding statement to each P-code can be found at the GHS Classification page.)

  • Anovulatory cycle

  • Carcinogenicity

  • Cardiac disorder

  • Cardiac failure

  • Cardiac failure congestive

  • Diabetes mellitus

  • Diabetic ketoacidosis

  • Foetor hepaticus

  • Hepatocellular injury

  • Insulin resistance

  • Liver disorder

  • Macroangiopathy

  • Type 1 diabetes mellitus

  • Type 2 diabetes mellitus

  • Weight decreased

  • Cardiac disorder (0)

  • Ischaemia (0)

  • Abdominal pain upper

  • Arthralgia

  • Asthenia

  • Back pain

  • Bronchitis

  • Cardiac failure

  • Cardiac failure congestive

  • Chest pain

  • Diabetes mellitus

  • Diarrhoea

  • Discomfort

  • Fatigue

  • Feeling abnormal

  • Gastroenteritis

  • Headache

  • Hypoglycaemia

  • Ill-defined disorder

  • Influenza

  • Injury

  • Malaise

  • Muscle spasms

  • Musculoskeletal discomfort

  • Myalgia

  • Oedema

  • Oedema peripheral

  • Pain in extremity

  • Pharyngitis

  • Respiratory tract infection

  • Sinusitis

  • Tooth abscess

  • Tooth disorder

  • Upper respiratory tract infection

  • Urinary tract infection

  • Visual impairment

  • Weight increased

    • (+/-)-5-[[4-[2-(5-Ethyl-2-pyridinyl)-ethoxy]phenyl]methyl]-2,4-thiazolidinedione (+/-)-5-[p-[2-(ethyl-2-pyridyl)ethoxy]benzyl]-2,4-thiazolidinedione 105355-27-9
    105390-47-4 111025-46-8 2,4-Thiazolidinedione, 5-((4-(2-(5-ethyl-2-pyridinyl)ethoxy)phenyl)methyl)-, (+-)-
    2,4-Thiazolidinedione, 5-[[4-[2-(5-ethyl-2-pyridinyl)ethoxy]phenyl]methyl]- (9CI) 2,4-Thiazolidinedione, 5-[[4-[2-(5-ethyl-2-pyridinyl)ethoxy]phenyl]methyl]-, (+/-)- 2,4-thiazolidinedione, 5-[[4-[2-(5-ethyl-2-pyridinyl)ethoxy]phenyl]methyl]-
    355P279 5-(4-(2-(5-ethyl-2-pyridyl)ethoxy)benzyl)-2,4-thiazolidinedione 5-(4-(2-(5-ethylpyridin-2-yl)ethoxy)benzyl)-thiazolidine-2,4-dione
    5-(4-(2-(5-ethylpyridin-2-yl)ethoxy)benzyl)thiazolidine-2,4-dione 5-({4-[2-(5-ethylpyridin-2-yl)ethoxy]phenyl}methyl)-1,3-thiazolidine-2,4-dione 5-[4-[2-(5-ETHYL-2-PYRIDYL)ETHOXY]BENZYL]-2,4-THIAZOLIDINEDIONE
    5-[4-[2-(5-Ethyl-2-pyridyl)ethoxy]benzyl]thiazolidine-2,4-dione 5-[4-[2-(5-ethyl-2-pyridyl) ethoxy]benzyl]-2,4-thiazolidinedione 5-[4-[2-(5-ethyl-2-pyridyl)eth-oxy]benzyl]-2,4-thiazolidinedione
    5-[[4-[2-(5-Ethyl-2-pyridinyl)ethoxy]phenyl]methyl-2,4-thiazolidinedione 5-[[4-[2-(5-ethyl-2-pyridinyl)ethoxy]phenyl]methyl]thiazolidine-2,4-dione 5-[[4-[2-(5-ethyl-2-pyridyl)ethoxy] phenyl]methyl]-2,4-thiazolidinedione
    5-[[4-[2-(5-ethylpyridin-2-yl)ethoxy]phenyl]methyl]-1,3-thiazolidine-2,4-dione 5-[[4-[2-(5-ethylpyridin-2-yl)ethoxy]phenyl]methyl]thiazolidine-2,4-dione 5-[[4-[2-[(5-ethyl-2-pyridyl)]ethoxy]phenyl]methyl]thiazolidine- 2,4-dione
    5-{4-[2-(5-ethyl-2-pyridyl)ethoxy]benzyl}-2,4-thiazolidinedione 5-{4-[2-(5-ethyl-2-pyridyl)ethoxy]benzyl}-2,4thiazolidinedione 5-{4-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl}-1,3-thiazolidine-2,4-dione
    5-{4-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl}-4-hydroxy-1,3-thiazol-2(5H)-one A801204 AB0004710
    AB00698454-10 AB00698454_11 AB00698454_12
    AB00698454_13 AB1004597 AB2000683
    AC-1021 ACT02635 AD-4833
    AK-56326 AKOS015894953 AKOS022109420
    API0009130 Actos Actos (TN)
    BBL029068 BCP26474 BDBM50103521
    BRD-A48430263-003-02-4 BRD-A48430263-003-06-5 BSPBio_002723
    C07675 C19H20N2O3S CCG-220107
    CHEBI:8228 CS-1700 CTK5B5876
    D08378 DB-027350 DB01132
    DTXSID3037129 Duetact FT-0601906
    FT-0645030 GTPL2694 Glustin
    HMS2089H14 HMS3651D09 HMS3712E16
    HS-0047 HSDB 7322 HY-13956
    HYAFETHFCAUJAY-UHFFFAOYSA-N J-002506 J-516181
    J10289 K-0703 KBio2_002103
    KBio2_004671 KBio2_007239 KBio3_001943
    KBioGR_001619 KBioSS_002103 KS-00000XMH
    LS-151327 MCULE-2346786634 MLS006011848
    NCGC00163128-01 NCGC00163128-02 NCGC00163128-03
    NCGC00163128-04 NCGC00163128-05 NCGC00163128-06
    NCGC00163128-07 NSC-758876 NSC758876
    Pharmakon1600-01504401 Pioglitazona Pioglitazona [INN-Spanish]
    Pioglitazone Pioglitazone (Actos) Pioglitazone [BAN:INN]
    Pioglitazone [INN:BAN] Pioglitazonum Pioglitazonum [INN-Latin]
    Pioglu Piozone Q417765
    RTX-010718 SB17323 SBI-0206791.P001
    SC-14147 SCHEMBL4121 SMR002204015
    SPBio_001897 SR-01000763737 SR-01000763737-5
    ST24044191 STL309607 STL373406
    SW197561-3 Spectrum2_001679 Spectrum3_001002
    Spectrum4_001130 Spectrum5_001480 Spectrum5_002067
    Spectrum_001623 U 72107 U 72107A
    U-72107 U72,107A Zactos
    [( inverted exclamation markA)-5-[[4-[2-(5-ethyl-2-pyridinyl) ethoxy] phenyl] methyl]-2,4-] thiazolidinedione monohydrochlorid [()-5-[[4-[2-(5-ethyl-2-pyridinyl) ethoxy] phenyl] methyl]-2,4-] thiazolidinedione monohydrochlorid pioglitazone (INN)
    pioglitazone-actos s2590

    DrugBank Name Pioglitazone
    DrugBank DB01132
    CAS Number 105355-27-9, 105390-47-4, 111025-46-8, 112529-15-4, 1134163-29-3, 1134163-31-7, 627502-58-3, 728045-10-1
    PubChem Compound 4829
    KEGG Compound ID C07675
    KEGG Drug D08378
    PubChem.Substance 46507136
    ChEBI 8228
    PharmGKB PA450970
    ChemSpider 4663
    BindingDB 50103521.0
    TTD DAP000272
    Wikipedia Pioglitazone
    DPD 12012

    1. Dykens et al. (2007)
    2. Chan et al. (2005)
    3. Brunmair et al. (2004)
    4. Vuda et al. (2016)