Search References Drug Actions/Targets About Access data Feedback
Sign In
mitontu@gmail.com
2021 MitoTox | (CC BY-NC 4.0)
Drug

D0488 | crizotinib

Molecular Formula C21H22Cl2FN5O
Molecular Weight 450.3
Structure
State solid
Clearance The mean apparent clearance (CL/F) of crizotinib was lower at steady state (60 L/hr) after 250 mg twice daily than that after a single 250 mg oral dose (100 L/hr), which was likely due to autoinhibition of CYP3A by crizotinib after multiple dosing.
Volume of distribution Mean volume of distribution (Vss) is 1772 L following intravenous administration of a 50 mg dose. This high volume of distribution suggest extensive distribution into tissue from plasma.
Route of elimination Following the administration of a single 250 mg radiolabeled crizotinib dose to healthy subjects, 63% and 22% of the administered dose was recovered in feces and urine, respectively. Unchanged crizotinib represented approximately 53% and 2.3% of the administered dose in feces and urine, respectively.
Protein binding Crizotinib is 91% bound to plasma protein. This is not affected by drug concentration.
Half life Plasma terminal half-life, patients = 42 hours
Absorption The peak serum concentration was reached in 4 to 6 hours following an oral single-dose administration. Steady state was reached within 15 days when a dose of 250 mg twice daily was administered. The mean absolute bioavailability was 43% (range of 32% to 66%) following a single 250 mg oral dose. When taken with high-fat meal, AUC and Cmax were reduced.

L

L01XE16 Crizotinib


[L01XE] Protein kinase inhibitors


[L01X] OTHER ANTINEOPLASTIC AGENTS


[L01] ANTINEOPLASTIC AGENTS


[L] Antineoplastic and immunomodulating agents

Toxicity Dose Time Species Model Method Action Positive criterion Reference
UNCOUPLING rat isolated liver mitochondria measurements of mitochondrial respiration; RST inhibition assay, RST uncoupling assay; IC 50ratio of glucose/galactose assay increase 53

Pictogram Signal Statements Precautionary Statement Codes
Danger

Aggregated GHS information provided by 71 companies from 4 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.


H317 (100%): May cause an allergic skin reaction [Warning Sensitization, Skin]


H318 (40.85%): Causes serious eye damage [Danger Serious eye damage/eye irritation]


H319 (57.75%): Causes serious eye irritation [Warning Serious eye damage/eye irritation]


H341 (100%): Suspected of causing genetic defects [Warning Germ cell mutagenicity]


H400 (59.15%): Very toxic to aquatic life [Warning Hazardous to the aquatic environment, acute 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, P272, P273, P280, P281, P302+P352, P305+P351+P338, P308+P313, P310, P321, P333+P313, P337+P313, P363, P391, P405, and P501; (The corresponding statement to each P-code can be found at the GHS Classification page.)


  • (R)-3-(1-(2,6-dichloro-3-fluorophenyl)ethoxy)-5-(1-(piperidin-4-yl)-1H-pyrazol-4-yl)pyridin-2-am ine (R)-3-(1-(2,6-dichloro-3-fluorophenyl)ethoxy)-5-(1-(piperidin-4-yl)-1H-pyrazol-4-yl)pyridin-2-amine (R)-3-[1-(2,6-Dichloro-3-fluoro-phenyl)-ethoxy]-5-(1-piperidin-4-yl-1H-pyrazol-4-yl)-pyridin-2-ylamine
    (R)-crizotinib 2-Pyridinamine, 3-((1R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy)-5-(1-(4-piperidinyl)-1H-pyrazol-4-yl)- 3-(1R)-1-(2,6-Dichloro-3-fluorophenyl)ethoxy-5-1-(4-piperidinyl)-1H-pyrazol-4-yl-2-Pyridinamine
    3-(2,6-dichloro-3-fluorobenzyloxy)-5-(1-(piperidin-4-yl)-1H-pyrazol-4-yl)pyridin-2-amine 3-[(1R)-1-(2,6-DICHLORO-3-FLUOROPHENYL)ETHOXY]-5-[1-(4-PIPERIDINYL)-1H-PYRAZOL-4-YL]PYRIDIN-2-AMINE 3-[(1R)-1-(2,6-Dichloro-3-fluorophenyl)ethoxy]-5-[1-(4-piperidinyl)-1H-pyrazol-4-yl]-2-pyridinamine
    3-[(1R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]-5-[ 3-[(1R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]-5-[1-(piperidin-4-yl)-1H-pyrazol-4-yl]pyridin-2-amine 3-[(1r)-1-(2,6-Dichloro-3-Fluorophenyl)ethoxy]-5-(1-Piperidin-4-Yl-1h-Pyrazol-4-Yl)pyridin-2-Amine
    3-[(R)-1-(2,6-Dichloro-3-fluoro-phenyl)-ethoxy]-5-(1-piperidin-4-yl-1H-pyrazol-4-yl)-pyridin-2-ylamine; 3-[1-(2,6-Dichloro-3-fluoro-phenyl)-ethoxy]-5-(1-piperidin-4-yl-1H-pyrazol-4-yl)-pyridin-2-ylamine 399P525
    53AH36668S 877399-52-5 877399-52-5, 877399-53-6 (acetate)
    AB0027203 ABP000131 AKOS015901233
    AKOS015995207 AMX10152 ANW-47749
    AOB2688 BB 0261738 BCPP000116
    BDBM50306682 BRD-K78431006-001-01-1 BRD-K78431006-001-03-7
    C21H22Cl2FN5O CHEBI:64310 CHEMBL601719
    CTK5F8952 Crizotinib Crizotinib (JAN/USAN/INN)
    Crizotinib (PF-02341066) Crizotinib (PF-2341066) Crizotinib [USAN:INN]
    Crizotinib, >=98% (HPLC) D09731 DB08865
    DTXSID701009329 EN002685 EX-A096
    FT-0665224 GS-6178 GTPL4903
    HY-50878 J-510370 KIN0000318
    KS-0000075X KTEIFNKAUNYNJU-GFCCVEGCSA-N NCGC00250400-01
    NCGC00250400-09 NCGC00250400-12 NSC-749005
    NSC749005 PB11015 PF 02341066
    PF 2341066 PF 2341066;(R)-3-[1-(2,6-Dichloro-3-fluoro-phenyl)-ethoxy]-5-(1-piperidin-4-yl-1H-pyrazol-4-yl)-pyridin-2-ylamine PF-02341066
    PF-02341066 (Crizotinib) PF-2341066 PF-2341066 (Crizotinib)
    PF-2341066 - Crizotinib PF-2341066(Crizotinib) PF-2341066,Crizotinib
    PF02341066 PF2341066 PubChem19322
    Q-3209 Q5186964 QCR-32
    SC-48062 SCHEMBL93829 SW202555-3
    SYN1139 TX-017903 UNII-53AH36668S
    VGH W9013 Xalkori
    Xalkori (TN) ZINC35902489 crizotinibum

    DrugBank Name crizotinib
    DrugBank DB08865
    CAS Number 877399-52-5, 877399-53-6
    PubChem Compound 11626560
    KEGG Drug D09731
    ChEBI 64310
    PharmGKB PA165946122