Tìm theo
Lapatinib
Các tên gọi khác (7 ) :
  • FMM
  • GW 572016
  • Lapatinib ditosylate
  • Lapatinib tosilate hydrate
  • N-(3-chloro-4-((3-Fluorophenyl)methoxy)phenyl)-6-(5-(((2-(methylsulfonyl)ethyl)amino)methyl)-2-furanyl)-4-quinazolinamine
  • N-{3-chloro-4-[(3-fluorobenzyl)oxy]phenyl}-6-[5-({[2-(methylsulfonyl)ethyl]amino}methyl)-2-furyl]-4-quinazolinamine
  • Tykerb
Thuốc điều trị ung thư
Thuốc Gốc
Small Molecule
CAS: 388082-78-8
ATC: L01XE07
ĐG : GlaxoSmithKline Inc. , http://www.gsk.com
CTHH: C29H26ClFN4O4S
PTK: 581.058
Lapatinib is an anti-cancer drug developed by GlaxoSmithKline (GSK) as a treatment for solid tumours such as breast and lung cancer. It was approved by the FDA on March 13, 2007, for use in patients with advanced metastatic breast cancer in conjunction with the chemotherapy drug Capecitabine. Lapatinib is human epidermal growth factor receptor type 2 (HER2/ERBB2) and epidermal growth factor receptor (HER1/EGFR/ERBB1) tyrosine kinases inhibitor. It binds to the intracellular phosphorylation domain to prevent receptor autophosphorylation upon ligand binding.
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C29H26ClFN4O4S
Phân tử khối
581.058
Monoisotopic mass
580.134731942
InChI
InChI=1S/C29H26ClFN4O4S/c1-40(36,37)12-11-32-16-23-7-10-27(39-23)20-5-8-26-24(14-20)29(34-18-33-26)35-22-6-9-28(25(30)15-22)38-17-19-3-2-4-21(31)13-19/h2-10,13-15,18,32H,11-12,16-17H2,1H3,(H,33,34,35)
InChI Key
InChIKey=BCFGMOOMADDAQU-UHFFFAOYSA-N
IUPAC Name
N-{3-chloro-4-[(3-fluorophenyl)methoxy]phenyl}-6-(5-{[(2-methanesulfonylethyl)amino]methyl}furan-2-yl)quinazolin-4-amine
Traditional IUPAC Name
lapatinib
SMILES
CS(=O)(=O)CCNCC1=CC=C(O1)C1=CC2=C(C=C1)N=CN=C2NC1=CC(Cl)=C(OCC2=CC(F)=CC=C2)C=C1
Độ hòa tan
2.23e-02 g/l
logP
5.4
logS
-4.4
pKa (strongest acidic)
15.99
pKa (Strongest Basic)
7.2
PSA
106.35 Å2
Refractivity
152.42 m3·mol-1
Polarizability
61.19 Å3
Rotatable Bond Count
11
H Bond Acceptor Count
7
H Bond Donor Count
2
Physiological Charge
1
Number of Rings
5
Bioavailability
0
MDDR-Like Rule
true
Dược Lực Học : Lapatinib is a small molecule and a member of the 4-anilinoquinazoline class of kinase inhibitors. An anti-cancer drug, lapatinib was developed by GlaxoSmithKline (GSK) as a treatment for solid tumours such as breast and lung cancer. It was approved by the FDA on March 13, 2007, for use in patients with advanced metastatic breast cancer in conjunction with the chemotherapy drug capecitabine.
Cơ Chế Tác Dụng : Lapatinib is an anti-cancer drug developed by GlaxoSmithKline (GSK) as a treatment for solid tumours such as breast and lung cancer. It was approved by the FDA on March 13, 2007, for use in patients with advanced metastatic breast cancer in conjunction with the chemotherapy drug Capecitabine. Lapatinib is human epidermal growth factor receptor type 2 (HER2/ERBB2) and epidermal growth factor receptor (HER1/EGFR/ERBB1) tyrosine kinases inhibitor. It binds to the intracellular phosphorylation domain to prevent receptor autophosphorylation upon ligand binding. Lapatinib is a 4-anilinoquinazoline kinase inhibitor of the intracellular tyrosine kinase domains of both epidermal growth factor receptor (HER1/EGFR/ERBB1) and human epidermal growth factor receptor type 2 (HER2/ERBB2)with a dissociation half-life of ≥300 minutes. Lapatinib inhibits ERBB-driven tumor cell growth in vitro and in various animal models. An additive effect was demonstrated in an in vitro study when lapatinib and 5-florouracil (the active metabolite of capecitabine) were used in combination in the 4 tumor cell lines tested. The growth inhibitory effects of lapatinib were evaluated in trastuzumab-conditioned cell lines. Lapatinib retained significant activity against breast cancer cell lines selected for long-term growth in trastuzumab-containing medium in vitro. These in vitro findings suggest non-cross-resistance between these two agents.
Dược Động Học :
▧ Absorption :
Absorption following oral administration of lapatinib is incomplete and variable.
▧ Protein binding :
Highly bound (>99%) to albumin and alpha-1 acid glycoprotein
▧ Metabolism :
Lapatinib undergoes extensive metabolism, primarily by CYP3A4 and CYP3A5, with minor contributions from CYP2C19 and CYP2C8 to a variety of oxidated metabolites, none of which accounts for more than 14% of the dose recovered in the feces or 10% of lapatinib concentration in plasma.
▧ Route of Elimination :
Lapatinib undergoes extensive metabolism, primarily by CYP3A4 and CYP3A5, with minor contributions from CYP2C19 and CYP2C8 to a variety of oxidated metabolites, none of which accounts for more than 14% of the dose recovered in the feces or 10% of lapatinib concentration in plasma.
▧ Half Life :
Single-dose terminal half life: 14.2 hours Effective multiple-dose half life: 24 hours
Độc Tính : There has been a report of one patient who took 3,000 mg of lapatinib for 10 days. This patient had grade 3 diarrhea and vomiting on day 10.
Chỉ Định : Indicated in combination with capecitabine for the treatment of patients with advanced or metastatic breast cancer whose tumors overexpress the human epidermal receptor type 2 (HER2) protein and who have received prior therapy including an anthracycline, a taxane, and trastuzuma.
Tương Tác Thuốc :
  • Artemether Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
  • Etravirine Lapatinib, when used concomitantly with etravirine (a strong CYP3A4 inducer), may experience a decrease in serum concentration. It is recommended to avoid this combination.
  • Lumefantrine Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
  • Pazopanib Lapatinib is a weak inhibitor of CYP3A4, BCRP, and p-glycoprotein and may increase exposure of pazopanib. AUC and Cmax increase by 50-60%.
  • Tacrolimus Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
  • Tamsulosin Lapatinib, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Lapatinib is initiated, discontinued, or dose changed.
  • Telithromycin Telithromycin may reduce clearance of Lapatinib. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Lapatinib if Telithromycin is initiated, discontinued or dose changed.
  • Thiothixene May cause additive QTc-prolonging effects. Increased risk of ventricular arrhythmias. Consider alternate therapy. Thorough risk:benefit assessment is required prior to co-administration.
  • Tolterodine Lapatinib may decrease the metabolism and clearance of Tolterodine. Adjust Tolterodine dose and monitor for efficacy and toxicity.
  • Topotecan The p-glycoprotein inhibitor, Lapatinib, may increase the bioavailability of oral Topotecan. A clinically significant effect is also expected with IV Topotecan. Concomitant therapy should be avoided.
  • Toremifene Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.
  • Tramadol Lapatinib may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance.
  • Trazodone The CYP3A4 inhibitor, Lapatinib, may increase Trazodone efficacy/toxicity by decreasing Trazodone metabolism and clearance. Monitor for changes in Trazodone efficacy/toxicity if Lapatinib is initiated, discontinued or dose changed.
  • Tretinoin The moderate CYP2C8 inhibitor, Lapatinib, may decrease the metabolism and clearance of oral Tretinoin. Monitor for changes in Tretinoin effectiveness and adverse/toxic effects if Lapatinib is initiated, discontinued to dose changed.
  • Trimipramine Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
  • Voriconazole Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of lapatinib by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of lapatinib if voriconazole is initiated, discontinued or dose changed.
  • Vorinostat Additive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
  • Ziprasidone Additive QTc-prolonging effects may increase the risk of severe arrhythmias. Concomitant therapy is contraindicated.
  • Zuclopenthixol Additive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
Liều Lượng & Cách Dùng : Tablet - Oral - 250 mg
Dữ Kiện Thương Mại
Giá thị trường
  • Biệt dược thương mại : Tykerb 250 mg tablet
    Giá bán buôn : USD >28.4
    Đơn vị tính : tablet
Nhà Sản Xuất
  • Công ty :
    Sản phẩm biệt dược : Tycerb
  • Công ty :
    Sản phẩm biệt dược : Tykerb
Đóng gói
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB01259
PubChem Compound
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=208908
PubChem Substance
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=46507141
KEGG Drug
http://www.genome.jp/dbget-bin/www_bget?drug:D04024
ChemSpider
http://www.chemspider.com/Chemical-Structure.181006.html
BindingDB
http://www.bindingdb.org/bind/chemsearch/marvin/MolStructure.jsp?monomerid=5445
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/0173-0752-00
PharmGKB
http://www.pharmgkb.org/drug/PA152241907
Wikipedia
http://en.wikipedia.org/wiki/Lapatinib
RxList
http://www.rxlist.com/cgi/generic/tykerb.htm
Drugs.com
http://www.drugs.com/cdi/lapatinib.html
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