Tìm theo
Crizotinib
Các tên gọi khác (7 ) :
  • (R)-Crizotinib
  • C-Met/Hepatocyte Growth Factor Receptor Tyrosine Kinase Inhibitor PF-02341066
  • C-Met/HGFR Tyrosine Kinase Inhibitor PF-02341066
  • Crizotinibum
  • MET Tyrosine Kinase Inhibitor PF-02341066
  • PF 2341066
  • PF-2341066
protein kinase inhibitors
Thuốc Gốc
Small Molecule
CAS: 877399-52-5
ATC: L01XE16
CTHH: C21H22Cl2FN5O
PTK: 450.337
Crizotinib an inhibitor of receptor tyrosine kinase for the treatment of non-small cell lung cancer (NSCLC). Verification of the presence of ALK fusion gene is done by Abbott Molecular's Vysis ALK Break Apart FISH Probe Kit. This verification is used to select for patients suitable for treatment. FDA approved in August 26, 2011.
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C21H22Cl2FN5O
Phân tử khối
450.337
Monoisotopic mass
449.11854397
InChI
InChI=1S/C21H22Cl2FN5O/c1-12(19-16(22)2-3-17(24)20(19)23)30-18-8-13(9-27-21(18)25)14-10-28-29(11-14)15-4-6-26-7-5-15/h2-3,8-12,15,26H,4-7H2,1H3,(H2,25,27)/t12-/m1/s1
InChI Key
InChIKey=KTEIFNKAUNYNJU-GFCCVEGCSA-N
IUPAC Name
3-[(1R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]-5-[1-(piperidin-4-yl)-1H-pyrazol-4-yl]pyridin-2-amine
Traditional IUPAC Name
crizotinib
SMILES
C[C@@H](OC1=CC(=CN=C1N)C1=CN(N=C1)C1CCNCC1)C1=C(Cl)C=CC(F)=C1Cl
Độ hòa tan
6.11e-03 g/l
logP
1.83
logS
-4.9
pKa (Strongest Basic)
10.12
PSA
77.99 Å2
Refractivity
128.43 m3·mol-1
Polarizability
45.43 Å3
Rotatable Bond Count
5
H Bond Acceptor Count
5
H Bond Donor Count
2
Physiological Charge
1
Number of Rings
4
Bioavailability
1
Rule of Five
true
Ghose Filter
true
Cơ Chế Tác Dụng : Crizotinib an inhibitor of receptor tyrosine kinase for the treatment of non-small cell lung cancer (NSCLC). Verification of the presence of ALK fusion gene is done by Abbott Molecular's Vysis ALK Break Apart FISH Probe Kit. This verification is used to select for patients suitable for treatment. FDA approved in August 26, 2011. Crizotinib is a tyrosine kinase receptor inhibitor. More specifically, it inhibits anaplastic lymphoma kinase (ALK), hepatocyte growth factor receptor (HGFR, c-MET), and Recepteur d'Origine Nantais (RON). Abnormalities in the ALK gene caused by mutations or translocations may lead to expression of oncogenic fusion proteins. In patients with NSCLC, they have the EML4-ALK gene. Crizotinib inhibits ALK tyrosine kinase which ultimately results in decreased proliferation of cells that carry the genetic mutation and tumour survivability.
Dược Động Học :
▧ 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.
▧ 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.
▧ Protein binding :
Crizotinib is 91% bound to plasma protein. This is not affected by drug concentration.
▧ Metabolism :
Crizotinib is metabolized by CYP3A4 and CYP3A5 in which these enzymes mediates the O-dealkylation of the drug.
▧ 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.
▧ Half Life :
Plasma terminal half-life, patients = 42 hours
▧ 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.
Chỉ Định : Crizotinib is used for the treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC) that is anaplastic-lymphoma kinase (ALK)-positive as detected by a FDA-approved test.
Tương Tác Thuốc :
  • Bosutinib Strong CYP3A4 inhibitors may increase levels of crizotinib. Consider alternative therapy.
  • Cisapride Concurrent use with drugs that prolong QTc interval is contraindicated.
  • Disopyramide Strong CYP3A4 inhibitors may increase levels of crizotinib. Consider alternative therapy.
  • Dronedarone Concurrent use with drugs that prolong QTc interval is contraindicated.
  • Etravirine Crizotinib, when administered concomitantly with etravirine (a strong CYP3A4 inducer), may experience a decrease in serum concentration. It is recommended to avoid this combination.
  • Fluticasone Propionate Concurrent use with crizotinib may prolong QTc interval. Consider alternative therapy.
  • Ketoconazole Strong CYP3A4 inhibitors may increase levels of crizotinib. Monitor concomitant therapy closely.
  • Lomitapide Strong CYP3A4 inhibitors may increase levels of crizotinib. Concomitant therapy is contraindicated.
  • Midazolam Strong CYP3A4 inhibitors may increase levels of crizotinib. Monitor concomitant therapy closely.
  • Midazolam Strong CYP3A4 inhibitors may increase levels of crizotinib. Monitor concomitant therapy closely.
  • Ondansetron Concurrent use with crizotinib may decrease QTc interval. Consider alternative therapy.
  • Quinidine Strong CYP3A4 inhibitors may increase levels of crizotinib. Consider alternative therapy.
  • Rifampicin Strong CYP3A4 inducers may decrease levels of crizotinib. Monitor concomitant therapy closely.
  • Rifampicin Strong CYP3A4 inducers may decrease levels of crizotinib. Monitor concomitant therapy closely.
  • Tacrolimus Strong CYP3A4 inhibitors may increase levels of crizotinib. Consider alternative therapy.
  • Thioridazine Concurrent use with drugs that prolong QTc interval is contraindicated.
Liều Lượng & Cách Dùng : Capsule - Oral - 200 mg, 250 mg
Dữ Kiện Thương Mại
Nhà Sản Xuất
  • Công ty : Pfizer
    Sản phẩm biệt dược : Xalkori
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB08865
KEGG Drug
http://www.genome.jp/dbget-bin/www_bget?drug:D09731
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/0069-8141-20
PharmGKB
http://www.pharmgkb.org/drug/PA165946122
Wikipedia
http://en.wikipedia.org/wiki/Crizotinib
RxList
http://www.rxlist.com/xalkori-drug.htm
Drugs.com
http://www.drugs.com/cdi/crizotinib.html
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