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Drug

D0266 | Glimepiride

Molecular Formula C24H34N4O5S
Molecular Weight 490.6
Structure
State solid
Clearance A single-dose, crossover, dose-proportionality (1, 2, 4, and 8 mg) study in normal subjects and from a single- and multiple-dose, parallel, dose proportionality (4 and 8 mg) study in patients with type 2 diabetes (T2D) were performed. In these studies, the total body clearance was 52.1 +/- 16.0 mL/min, 48.5 +/- 29.3 mL/min in patients with T2D given a single oral dose, and 52.7 +/- 40.3 mL/min in patients with T2D given multiple oral doses [F4540]. Following intravenous dosing in healthy subjects, the total body clearance was 47.8 mL/min [FDA Label].
Volume of distribution Following intravenous dosing in healthy subjects, the volume of distribution was 8.8 L (113 mL/kg) [FDA Label].
Route of elimination Following oral administration of glimepiride in healthy male subjects, approximately 60% of the total radioactivity was recovered in the urine in 7 days, with M1 and M2 accounting for 80-90% of the total radioactivity recovered in the urine. The ratio of M1 to M2 was approximately 3:2 in two subjects and 4:1 in one subject [FDA Label]. Approximately 40% of the total radioactivity was recovered in feces where M1 and M2 accounted for about 70% of the radioactivity and a ratio of M1 to M2 being 1:3. No parent drug was recovered from urine or feces [FDA Label].
Protein binding Plasma protein binding of glimepiride is greater than 99.5% [FDA Label].
Half life The elimination half-life of glimepiride is approximately 5 to 8 hours [A177715], which can increase up to 9 hours following multiple doses [A177709].
Absorption Glimepiride is completely absorbed after oral administration within 1 hour of administration with a linear pharmacokinetics profile [A177703]. Following administration of a single oral dose of glimepiride in healthy subjects and with multiple oral doses with type 2 diabetes, the peak plasma concentrations (Cmax) were reached after 2 to 3 hours post-dose [FDA Label]. Accumulation does not occur after multiple doses [A177703]. When glimepiride was given with meals, the time to reach Cmax was increased by 12% while the mean and AUC (area under the curve) were decreased by 8 to 9%, respectively [F4540]. In a pharmacokinetic study of Japanese patients with T2DM, Cmax value in once-daily dose was higher than those in twice-daily doses [A177724]. The absolute bioavailability of glimepiride is reported to be complete following oral administration [A177721].

A

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

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

A10BB12 Glimepiride


[A10BB] Sulfonylureas


[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
MEMBRANE POTENTIAL 94.6 µM 30 mins mouse liver mitochondria Rh123 fluorescence (excitation 485 nm, emission 535 nm) are recorded using a fluorescence multi-well plate reader (mCICCP (20 µM) treatments was considered as the 100% baseline for ΔΨm loss) decrease EC20 36
RESPIRATION 16.6 µM 60 mins mouse liver mitochondria Oxygen consumption was monitored with 50nM MitoXpress ( an oxygen-sensitive phosphorescent dye) using a spectrofluorimeter (Tecan Infinite 200; λExcitation 380nm; λEmission 650nm). Rotenone (2µM) was used as 100% baseline for complex I inhibition. decrease EC20 36
RESPIRATION ND 60 mins mouse liver mitochondria Oxygen consumption was monitored with 50nM MitoXpress ( an oxygen-sensitive phosphorescent dye) using a spectrofluorimeter (Tecan Infinite 200; λExcitation 380nm; λEmission 650nm). Oligomycin A (1µM) was used as 100% baseline for complex II inhibition. Negative EC20 36
SWELLING ND 30 mins mouse liver mitochondria swelling assay: Absorbance at 545 nm using a fluorescence multi-well plate reader (CaCl2 (50 µM) was considered as the 100% baseline for the swelling ) Negative EC20 36

Target Dose Time Species Model Method Action Positive criterion Reference
NADH:ubiquinone reductase 16.6 µM 60 mins mouse liver mitochondria Oxygen consumption was monitored with 50nM MitoXpress ( an oxygen-sensitive phosphorescent dye) using a spectrofluorimeter (Tecan Infinite 200; λExcitation 380nm; λEmission 650nm). Rotenone (2µM) was used as 100% baseline for complex I inhibition. inhibit EC20 36
Succinate dehydrogenase ND 60 mins mouse liver mitochondria Oxygen consumption was monitored with 50nM MitoXpress ( an oxygen-sensitive phosphorescent dye) using a spectrofluorimeter (Tecan Infinite 200; λExcitation 380nm; λEmission 650nm). Oligomycin A (1µM) was used as 100% baseline for complex II inhibition. Negative EC20 36
Cytochrome c > 800 µM 30 mins mouse liver mitochondria Cytochrome c release was evaluated using ELISA kit ( 20 µg/ml Alamethicin was used as 100% baseline) release EC20 36

Pictogram Signal Statements Precautionary Statement Codes
Danger

Aggregated GHS information provided by 6 companies from 6 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.


H301 (50%): Toxic if swallowed [Danger Acute toxicity, oral]


H315 (16.67%): Causes skin irritation [Warning Skin corrosion/irritation]


H319 (83.33%): Causes serious eye irritation [Warning Serious eye damage/eye irritation]


H331 (50%): Toxic if inhaled [Danger Acute toxicity, inhalation]


H361 (66.67%): Suspected of damaging fertility or the unborn child [Warning Reproductive toxicity]


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, P270, P271, P280, P281, P301+P310, P302+P352, P304+P340, P305+P351+P338, P308+P313, P311, P321, P330, P332+P313, P337+P313, P362, P403+P233, P405, and P501; (The corresponding statement to each P-code can be found at the GHS Classification page.)

  • Blood glucose decreased

  • Coma

  • Diabetic ketoacidosis

  • Hyperglycaemia

  • Hypoglycaemia

  • Nephropathy

  • Neuropathy peripheral

  • Obesity

  • Retinal disorder

  • Type 1 diabetes mellitus

  • Type 2 diabetes mellitus

  • Weight decreased

  • Asthenia

  • Dizziness

  • Headache

  • Influenza

  • Injury

  • Nausea

    • 1-((p-(2-(3-Ethyl-4-methyl-2-oxo-3-pyrroline-1-carboxamido)ethyl)phenyl)sulfonyl)-3-(trans-4-methylcyclohexyl)urea 1-[[4-[2-[[(3-Ethyl-4-methyl-2-oxo-2,3-dihydro-1H-pyrrol-1-yl)carbonyl]amino]ethyl]phenyl]sulphonyl]-3-(cis-4-methylcyclohexyl)urea (cis-Glimepiride) 1-{[4-(2-{[(3-ethyl-4-methyl-2-oxo-2,5-dihydro-1H-pyrrol-1-yl)carbonyl]amino}ethyl)phenyl]sulfonyl}-3-(trans-4-methylcyclohexyl)urea
    1H-Pyrrole-1-carboxamide, 2,5-dihydro-3-ethyl-4-methyl-N-(2-(4-(((((4-methylcyclohexyl)amino)carbonyl)amino)sulfonyl)phenyl)ethyl)-2-oxo-, trans- 1H-Pyrrole-1-carboxamide, 3-ethyl-2,5-dihydro-4-methyl-N-(2-(4-(((((4-methylcyclohexyl)amino)carbonyl)amino)sulfonyl)phenyl)ethyl)-2-oxo-, trans- 24T6XIR2MZ
    3-ETHYL-4-METHYL-N-(4-(N-((1R,4R)-4-METHYLCYCLOHEXYLCARBAMOYL)SULFAMOYL)PHENETHYL)-2-OXO-2,5-DIHYDRO-1H-PYRROLE-1-CARBOXAMIDE 3-Ethyl-2,5-dihydro-4-methyl-N-[2-[4-[[[[(trans-4-methylcyclohexyl)amino]carbonyl]amino]sulfonyl]phenyl]ethyl]-2-oxo-1H-pyrrole-1-carboxamide 3-Ethyl-4-Methyl-N-[2-(4-{[(Cis-4-Methylcyclohexyl)carbamoyl]sulfamoyl}phenyl)ethyl]-2-Oxo-2,5-Dihydro-1h-Pyrrole-1-Carboxamide
    3-Ethyl-4-methyl-N-[2-[4-[[3-(4-methylcyclohexyl)ureido]sulfonyl]phenyl]ethyl]-2-oxo-2,5-dihydro-1H-pyrrole-1-carboxamide 3-Ethyl-4-methyl-N-{2-[4-({[(1r,4r)-4-methylcyclohexyl]carbamoyl}sulfamoyl)phenyl]ethyl}-2-oxo-2,5-dihydro-1H-pyrrole-1-carboxamide 3-ethyl-4-methyl-2-oxo-N-(2-{4-[({[(1r,4r)-4-methylcyclohexyl]carbamoyl}amino)sulfonyl]phenyl}ethyl)-2,5-dihydro-1H-pyrrole-1-carboxamide
    3-ethyl-4-methyl-N-(4-(N-(((1r,4r)-4-methylcyclohexyl)carbamoyl)sulfamoyl)phenethyl)-2-oxo-2,5-dihydro-1H-pyrrole-1-carboxamide 3-ethyl-4-methyl-N-(4-(N-((1r,4r)-4-methylcyclohexylcarbamoyl) 3-ethyl-4-methyl-N-(4-(N-((4-methylcyclohexyl)carbamoyl)sulfamoyl)phenethyl)-2-oxo-2,5-dihydro-1H-pyrrole-1-carboxamide
    3-ethyl-4-methyl-N-(4-(N-((trans-4-methylcyclohexyl)carbamoyl)sulfamoyl)phenethyl)-2-oxo-2,5-dihydro-1H-pyrrole-1-carboxamide 3-ethyl-4-methyl-N-[2-(4-{[(4-methylcyclohexyl)carbamoyl]sulfamoyl}phenyl)ethyl]-2-oxo-2,5-dihydro-1H-pyrrole-1-carboxamide 3-ethyl-4-methyl-N-[2-(4-{[(trans-4-methylcyclohexyl)carbamoyl]sulfamoyl}phenyl)ethyl]-2-oxo-2,5-dihydro-1H-pyrrole-1-carboxamide
    3-ethyl-4-methyl-N-[2-[4-[(4-methylcyclohexyl)carbamoylsulfamoyl]phenyl]ethyl]-2-oxo-5H-pyrrole-1-carboxamide 3-ethyl-4-methyl-N-{2-[4-({[(4-methylcyclohexyl)carbamoyl]amino}sulfonyl)phenyl]ethyl}-2-oxo-2,5-dihydro-1H-pyrrole-1-carboxamide 3-ethyl-4-methyl-n-(4-(n-((1r,4r)-4-methylcyclohexylcarbamoyl)sulfamoyl)phenethyl)-2-oxo-2,5-dihydro
    4-ethyl-3-methyl-N-[2-[4-[(4-methylcyclohexyl)carbamoylsulfamoyl]phenyl]ethyl]-5-oxo-2H-pyrrole-1-carboxamide 46931-EP2269989A1 46931-EP2270011A1
    46931-EP2272825A2 46931-EP2272841A1 46931-EP2275414A1
    46931-EP2287165A2 46931-EP2287166A2 46931-EP2292620A2
    46931-EP2295406A1 46931-EP2295422A2 46931-EP2298769A1
    46931-EP2298772A1 46931-EP2298776A1 46931-EP2301936A1
    46931-EP2305648A1 46931-EP2308839A1 46931-EP2308847A1
    46931-EP2308878A2 46931-EP2311822A1 479G971
    684286-46-2 6KY687524K 93479-97-1
    AB00513874 AB00513874-06 AB00513874-08
    AB00513874-09 AB00513874_10 AB00513874_11
    AB0073063 AB07644 AC-476
    AK164454 AKOS015894919 AKOS015969663
    AOB5663 AT-6093 Amarel
    Amaryl Amaryl (TN) BCP05331
    BCP9000728 BDBM50237590 BPBio1_000751
    BRD-K34776109-001-03-4 BRD-K42693031-001-01-8 BRN 5365754
    BSPBio_000681 C07669 CAS-93479-97-1
    CCG-101156 CCRIS 7083 CHEBI:5383
    CHEBI:92609 CHEMBL1481 CHEMBL149223
    CPD000466368 CS-1844 CTK8E7555
    D00593 DB00222 DSSTox_CID_20675
    DSSTox_GSID_40675 DSSTox_RID_79534 DTXSID5040675
    Endial FT-0626713 FT-0668978
    FT-0696605 G0395 GLIMPERIDE
    GTPL6820 Glemax Glimepirid
    Glimepirida Glimepirida [Spanish] Glimepiride (JP17/USP/INN)
    Glimepiride [USAN:BAN:INN] Glimepiride [USAN:USP:INN:BAN] Glimepiride for system suitability, European Pharmacopoeia (EP) Reference Standard
    Glimepiride, >=98% (HPLC), solid Glimepiride, British Pharmacopoeia (BP) Reference Standard Glimepiride, European Pharmacopoeia (EP) Reference Standard
    Glimepiride, United States Pharmacopeia (USP) Reference Standard Glimepiride, cis- Glimepiride,(S)
    Glimepiridum Glimepiridum [Latin] Glimepride
    Glimer Glista OD Glorion
    Glymepirid HMS1570C03 HMS2052L03
    HMS2090K18 HMS2097C03 HMS2235L07
    HMS3269A09 HMS3372O07 HMS3394L03
    HMS3413K06 HMS3654F17 HMS3677K06
    HMS3714C03 HOE 490 HOE490
    HY-B0104 Hoe-490 KS-5238
    LS-136752 MFCD00878417 MLS000759495
    MLS001076674 MLS001401419 MLS003915622
    MLS006011260 N'-{[4-(2-{[(3-ethyl-4-methyl-2-oxo-2,5-dihydro-1H-pyrrol-1-yl)carbonyl]amino}ethyl)phenyl]sulfonyl}-N-(4-methylcyclohexyl)carbamimidic acid N-[4-[2-(3-ethyl-4-methyl-2-oxo-3-pyrroline-1-carboxamido)-ethyl]-benzenesulfonyl]-N'-4-methylcyclohexylurea
    NC00406 NCGC00016960-01 NCGC00016960-02
    NCGC00016960-03 NCGC00016960-04 NCGC00016960-05
    NCGC00016960-07 NCGC00161404-01 NCGC00161404-02
    NCGC00181757-01 NCGC00371061-06 NSC-759809
    NSC759809 Niddaryl Oprea1_382896
    Pharmakon1600-01504915 Prestwick0_000651 Prestwick1_000651
    Prestwick2_000651 Prestwick3_000651 Q-201158
    Q27253874 Q425027 Roname
    SAM001246710 SC-13775 SC-46287
    SCHEMBL14371714 SCHEMBL14965363 SCHEMBL16084
    SCHEMBL16086 SCHEMBL8738802 SMR000466368
    SMR001550123 SPBio_002602 SR-05000001508
    SR-05000001508-1 SR-05000001508-2 SR-05000001508-3
    STL451059 STL453194 SW196369-4
    Solosa Sugral TX-017626
    Tox21_110713 Tox21_110713_1 Trans-3-Ethyl-2,5-dihydro-4-methyl-N-[2-[4-[[[[(4-methylcyclohexyl)amino]carbonyl]amino]sulfonyl]phenyl]ethyl]-2-oxo-1H-pyrrole-1-carboxamide
    UNII-24T6XIR2MZ UNII-6KY687524K Vitaimin E
    WIGIZIANZCJQQY-RUCARUNLSA-N WIGIZIANZCJQQY-UHFFFAOYSA-N ZINC100001976
    ZINC100070954 ZINC537791 cis-Glimepiride
    gimepiride glimepiride s1344
    sulfamoyl)phenethyl)-2-oxo-2,5-dihydro-1H-pyrrole-1-carboxamide trans-3-Ethyl-2,5-dihydro-4-methyl-N-[2-[4-[[[[(4-methyl cyclohexyl)amino]carbonyl]amino]sulfonyl]phenyl]ethyl]-2-oxo-1H-pyrrole-1-carboxamide trans-3-Ethyl-2,5-dihydro-4-methyl-N-[2-[4-[[[[trans-4-methylcyclohexyl)amino]carbonyl]amino]sulfonyl]phenyl]ethyl]-2-oxo-1H-pyrrole-1-carboxyamide

    DrugBank Name Glimepiride
    DrugBank DB00222
    CAS Number 1406-18-4, 684286-46-2, 93479-97-1
    PubChem Compound 3476
    KEGG Compound ID C07669
    KEGG Drug D00593
    PubChem.Substance 46508842
    ChEBI 5383
    PharmGKB PA449761
    ChemSpider 16740595
    TTD DAP000132
    Wikipedia Glimepiride
    DPD 12597