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Drug

D0108 | Rosiglitazone

Molecular Formula C18H19N3O3S
Molecular Weight 357.4
Structure
State solid
Clearance * Oral clearance (CL) = 3.03 ± 0.87 L/hr [1 mg Fasting] * Oral CL = 2.89 ± 0.71 L/hr [2 mg Fasting] * Oral CL = 2.85 ± 0.69 L/hr [8 mg Fasting] * Oral CL = 2.97 ± 0.81 L/hr [8 mg Fed] * 3.15 L/hr [Population mean, Pediatric patients]
Volume of distribution * 17.6 L [oral volume of distribution Vss/F] * 13.5 L [population mean, pediatric patients]
Route of elimination Following oral or intravenous administration of [14C]rosiglitazone maleate, approximately 64% and 23% of the dose was eliminated in the urine and in the feces, respectively.
Protein binding 99.8% bound to plasma proteins, primarily albumin.
Half life 3-4 hours (single oral dose, independent of dose)
Absorption The absolute bioavailability of rosiglitazone is 99%. Peak plasma concentrations are observed about 1 hour after dosing. Administration of rosiglitazone with food resulted in no change in overall exposure (AUC), but there was an approximately 28% decrease in C<sub>max</sub> and a delay in T<sub>max</sub> (1.75 hours). These changes are not likely to be clinically significant; therefore, rosiglitazone may be administered with or without food. Maximum plasma concentration (Cmax) and the area under the curve (AUC) of rosiglitazone increase in a dose-proportional manner over the therapeutic dose range.
Trade names Avandia
Description thiazolidinedione class of anti-diabetic drug; PPARgamma agonist

A

A10BG02 Rosiglitazone


[A10BG] Thiazolidinediones


[A10B] BLOOD GLUCOSE LOWERING DRUGS, EXCL. INSULINS


[A10] DRUGS USED IN DIABETES


[A] Alimentary tract and metabolism

A10BD04 Glimepiride and rosiglitazone


[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

A10BD03 Metformin and rosiglitazone


[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 10–50 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. Negative 331
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
UNCOUPLING increase 7
RESPIRATION 1uM 24 and 48 hours Murine 3T3-L1 adipocytes differentiated 96-well BD Oxygen Biosensor System plates increase 179
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 increase EC50 7
BASAL RESPIRATION 10 mM zebrafish XFe24 Extracellular Flux Analyzer Negative 88
BASAL RESPIRATION 10 mM zebrafish XFe24 Extracellular Flux Analyzer Negative 88
ELECTRON TRANSPORT CHAIN 50 μM bovine heart mitochondria Measurement of complex I activity Negative p < 0.05 3
ELECTRON TRANSPORT CHAIN 50 μM bovine heart mitochondria Measurement of complex II + III activity Negative p < 0.05 3
ELECTRON TRANSPORT CHAIN 50 μM bovine heart mitochondria Measurement of complex II + III activity Negative p < 0.05 3
ELECTRON TRANSPORT CHAIN 50 μM bovine heart mitochondria Measurement of complex IV activity Negative p < 0.05 3
ELECTRON TRANSPORT CHAIN 50 μM bovine heart mitochondria Measurement of complex V activity Negative p < 0.05 3
ELECTRON TRANSPORT CHAIN decrease 35
ELECTRON TRANSPORT CHAIN decrease 7
ELECTRON TRANSPORT CHAIN inhibit 197
TCA 1uM 24 and 48 hours Murine adipocytes Citrate Synthase Activity affect 179
ECAR 100 μM 2 minutes human HepG2 Measurement of ECAR Negative EC50 7
ECAR > 100 μM 2 minutes feline cardiomyocytes Measurement of ECAR increase EC50 7
GLUCOSE GALACTOSE IC50 RATIO 290.3 ± 16.7, 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
MASS 1uM 24 and 48 hours Murine adipocytes Mitochondrial Staining and Quantification affect 179
BIOGENESIS 1, 2, 4, 7, 24, and 48 hrs Murine differentiated 3T3-L1 and C3H/10T1/2 adipocytes increase 179

Target Dose Time Species Model Method Action Positive criterion Reference
NADH:ubiquinone reductase 50 μM bovine heart mitochondria Measurement of complex I activity Negative p < 0.05 3
NADH:ubiquinone reductase inhibitor 35
NADH:ubiquinone reductase inhibitor 7
Succinate dehydrogenase 50 μM bovine heart mitochondria Measurement of complex II + III activity Negative p < 0.05 3
Quinol--cytochrome-c reductase 50 μM bovine heart mitochondria Measurement of complex II + III activity Negative p < 0.05 3
Cytochrome c oxidase 50 μM bovine heart mitochondria Measurement of complex IV activity Negative p < 0.05 3
ATP synthase 50 μM bovine heart mitochondria Measurement of complex V activity Negative p < 0.05 3
Citrate synthase, mitochondrial 1uM 24 and 48 hours Murine adipocytes Citrate Synthase Activity not specified 179

Pictogram Signal Statements Precautionary Statement Codes
Warning

The GHS information provided by 1 company from 1 notification to the ECHA C&L Inventory.


H319 (100%): Causes serious eye irritation [Warning Serious eye damage/eye irritation]


H361 (100%): Suspected of damaging fertility or the unborn child [Warning Reproductive toxicity]


H410 (100%): Very toxic to aquatic life with long lasting effects [Warning Hazardous to the aquatic environment, long-term hazard]


 P201, P202, P264, P273, P280, P281, P305+P351+P338, P308+P313, P337+P313, P391, P405, and P501; (The corresponding statement to each P-code can be found at the GHS Classification page.)
Warning

Aggregated GHS information provided by 2 companies from 2 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.


H315 (50%): Causes skin irritation [Warning Skin corrosion/irritation]


H319 (100%): Causes serious eye irritation [Warning Serious eye damage/eye irritation]


H335 (50%): May cause respiratory irritation [Warning Specific target organ toxicity, single exposure


Respiratory tract irritation]


H361 (50%): Suspected of damaging fertility or the unborn child [Warning Reproductive toxicity]


H410 (50%): Very toxic to aquatic life with long lasting effects [Warning Hazardous to the aquatic environment, long-term hazard]


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.


 P201, P202, P261, P264, P271, P273, P280, P281, P302+P352, P304+P340, P305+P351+P338, P308+P313, P312, P321, P332+P313, P337+P313, P362, P391, P403+P233, P405, and P501; (The corresponding statement to each P-code can be found at the GHS Classification page.)

  • Diabetes mellitus

  • Diabetic ketoacidosis

  • Insulin resistance

  • Type 1 diabetes mellitus

  • Type 2 diabetes mellitus

  • Weight decreased

  • Anaemia (0.071)

  • Arthralgia

  • Asthenia

  • Back pain

  • Diarrhoea

  • Fatigue

  • Headache

  • Hyperglycaemia

  • Hypertension

  • Hypoglycaemia

  • Musculoskeletal discomfort

  • Nasopharyngitis

  • Sinusitis

  • Upper respiratory tract infection

    • (+/-)-5-[p-[2-(methyl-2-pyridylamino)ethoxy]benzyl]-2,4-thiazolidinedione (RS)-5-{4-[2-(Methyl-2-pyridylamino)ethoxy]benzyl}-2,4-thiazolidinedion 122320-73-4
    155141-29-0 2,4-Thiazolidinedione, 5-((4-(2-(methyl-2-pyridinylamino)ethoxy)phenyl)methyl)- 2,4-Thiazolidinedione, 5-004-02-((((methyl-2-pyridinylamino)ethoxy)phenyl)methyl)-
    2,4-Thiazolidinedione, 5-[[4-[2-(methyl-2-pyridinylamino)ethoxy]phenyl]methyl]- (9CI) 2,4-thiazolidinedione, 5-[[4-[2-(methyl-2-pyridinylamino)ethoxy]phenyl]methyl]- 20R734
    4CA-1110 5-((4-(2-(methyl-2-pyridinylamino)ethoxy)phenyl)methyl)-2,4-thiazolidinedione 5-((4-(2-Methyl-2-(pyridinylamino)ethoxy)phenyl)methyl)-2,4-thiazolidinedione-2-butenedioate
    5-(4-(2-(Methyl(pyridin-2-yl)amino)ethoxy)benzyl)thiazolidine-2,4-dione 5-(4-{2-[methyl(pyridin-2-yl)amino]ethoxy}benzyl)-1,3-thiazolidine-2,4-dione 5-[4-[2-(N-Methyl-N-(2-pyridyl)amino)ethoxy]benzyl]thiazolidine-2,4-dione
    5-[4-[2-(N-Methyl-N-(2-pyridyl)amino)ethoxy]benzyl]thiazolidine-2,4dione 5-[4-[2-(N-methyl-N-(2-pyridyl)amino)ethoxy]benzyl] thiazolidine-2,4-dione 5-[4-[2-[Methyl(2-pyridyl)amino]ethoxy]benzyl]thiazolidine-2,4-dione
    5-[4-[2-[N-methyl-N-(2-pyridyl)amino)ethoxy]benzyl]thiazolidine-2,4-dione 5-[4-[2-[N-methyl-N-(2-pyridyl)amino]ethoxy]phenyl methyl]thiazolidine-2,4-dione 5-[[4-[2-(Methyl-2-pyridinylamino)e thoxy]phenyl]methyl]-2,4-thiazolidinedione
    5-[[4-[2-(methyl-(2-pyridyl)amino)ethoxy]phenyl]methyl] thiazolidine-2,4-dione 5-[[4-[2-(methyl-2-pyridinylamino) ethoxy]phenyl]methyl]-2,4-thiazolidinedione 5-[[4-[2-(methyl-2-pyridinylamino)ethoxy]-phenyl]methyl]-2,4-thiazolidine-dione
    5-[[4-[2-(methyl-2-pyridinylamino)ethoxy]phenyl]methyl]-2,4-thiazolidinedione 5-[[4-[2-(methyl-pyridin-2-ylamino)ethoxy]phenyl]methyl]-1,3-thiazolidine-2,4-dione 6P-065
    AB0011992 AB00698473-15 AB00698473-17
    AB00698473-18 AB00698473-19 AB00698473_20
    AB00698473_21 AB00698473_22 AB00698473_23
    AB2000652 AC-3459 ACT04332
    AK-72839 AKOS015894872 ANW-44906
    API0006964 AX8017813 Avandamet
    Avandaryl Avandia Avandia;BRL-49653
    BBL029079 BCP03047 BCP0726000232
    BCP9000017 BDBM50030474 BG0432
    BR-72839 BRD-A97437073-001-02-3 BRD-A97437073-001-03-1
    BRD-A97437073-001-04-9 BRL49653 BSPBio_002693
    Brl 49653 Brl-49653 C-20817
    C18H19N3O3S CAS-122320-73-4 CC-34292
    CCG-39102 CHEBI:50122 CS-1088
    CTK8B4395 D08491 DB00412
    DSSTox_CID_17131 DSSTox_GSID_37131 DSSTox_RID_79303
    DTXSID7037131 FT-0602578 GP6434
    GTPL1056 Gaudil (TN) HMS1922J11
    HMS2094O13 HMS3649G08 HMS3656K16
    HMS3744M11 HSDB 7555 HY-17386
    IDMB (1uM BRL49653, 1uM Dexamethasone, 0.5uM IBMX, 10ug/mL Insulin) J10213 KBio2_002183
    KBio2_004751 KBio2_007319 KBio3_001913
    KBioGR_001609 KBioSS_002183 KS-00000IPU
    KSC914G9L LS-151340 MCULE-8293284864
    MFCD00871760 MP-0331 NCGC00095124-01
    NCGC00095124-02 NCGC00095124-03 NCGC00095124-04
    NCGC00095124-05 NCGC00095124-06 NCGC00095124-08
    NSC-758698 NSC758698 Pharmakon1600-01504263
    Q-201681 Q424771 R0106
    RTC-064102 Rezult Rosi
    Rosigilitazone Rosiglitazon Rosiglitazone (INN)
    Rosiglitazone [INN:BAN] Rosiglitazone base Rosiglitazone, >=98% (HPLC)
    Rosiglitazone-Avandia Rosiglizole S00306
    S2556 SB17326 SC-19017
    SCHEMBL14383595 SCHEMBL5169 SPBio_001142
    SPECTRUM1504263 SR-01000763023 SR-01000763023-12
    SR-01000763023-5 SR-01000763023-6 ST24029274
    STL350047 SW197573-6 Spectrum2_001241
    Spectrum3_000997 Spectrum4_001125 Spectrum5_001464
    Spectrum_001703 TDZ 01 Tox21_111434
    Tox21_111434_1 VA11695 YASAKCUCGLMORW-UHFFFAOYSA-N
    rosiglitazona rosiglitazone rosiglitazone (Avandia)
    rosiglitazonum

    DrugBank Name Rosiglitazone
    DrugBank DB00412
    CAS Number 1217260-35-9, 122320-73-4, 155141-29-0, 302543-62-0, 316371-83-2, 316371-84-3
    PubChem Compound 77999
    KEGG Drug D08491
    PubChem.Substance 46504556
    ChEBI 50122
    PharmGKB PA451283
    ChemSpider 70383
    BindingDB 50030474.0
    TTD DAP000271
    Wikipedia Rosiglitazone
    HET BRL
    DPD 11925

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