Tìm theo
Etoposide
Các tên gọi khác (18 ) :
  • (-)-Etoposide
  • 4-Demethylepipodophyllotoxin beta-D-ethylideneglucoside
  • 4'-Demethylepipodophyllotoxin 9-(4,6-O-(R)-ethylidene-beta-D-glucopyranoside)
  • 9-((4,6-O-Ethylidine-beta-D-glucopyranosyl)oxy)-5,8,8a,9-tetrahydro-5-(4-hydroxy-3,4-dimethyloxyphenyl)furo(3',4'':6,7)naptho-(2,3-D)-1,3-dioxol-6(5ah)-one
  • EPE
  • EPEG
  • Epipodophyllotoxin
  • Eposin
  • Etopophos
  • Etoposid
  • Etoposide
  • Etoposido
  • Etoposidum
  • Lastet
  • Toposar
  • trans-Etoposide
  • Vepesid
  • VP-16
Thuốc chống ung thư và tác động vào hệ thống miễn dịch
Thuốc Gốc
Small Molecule
CAS: 33419-42-0
ATC: L01CB01
ĐG : APP Pharmaceuticals , http://www.apppharma.com
CTHH: C29H32O13
PTK: 588.5566
A semisynthetic derivative of podophyllotoxin that exhibits antitumor activity. Etoposide inhibits DNA synthesis by forming a complex with topoisomerase II and DNA. This complex induces breaks in double stranded DNA and prevents repair by topoisomerase II binding. Accumulated breaks in DNA prevent entry into the mitotic phase of cell division, and lead to cell death. Etoposide acts primarily in the G2 and S phases of the cell cycle. [PubChem]
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C29H32O13
Phân tử khối
588.5566
Monoisotopic mass
588.18429111
InChI
InChI=1S/C29H32O13/c1-11-36-9-20-27(40-11)24(31)25(32)29(41-20)42-26-14-7-17-16(38-10-39-17)6-13(14)21(22-15(26)8-37-28(22)33)12-4-18(34-2)23(30)19(5-12)35-3/h4-7,11,15,20-22,24-27,29-32H,8-10H2,1-3H3/t11-,15+,20-,21-,22+,24-,25-,26-,27-,29+/m1/s1
InChI Key
InChIKey=VJJPUSNTGOMMGY-MRVIYFEKSA-N
IUPAC Name
(10R,11R,15R,16S)-16-{[(2R,4aR,6R,7R,8R,8aS)-7,8-dihydroxy-2-methyl-hexahydro-2H-pyrano[3,2-d][1,3]dioxin-6-yl]oxy}-10-(4-hydroxy-3,5-dimethoxyphenyl)-4,6,13-trioxatetracyclo[7.7.0.0^{3,7}.0^{11,15}]hexadeca-1(9),2,7-trien-12-one
Traditional IUPAC Name
(-)-etoposide
SMILES
[H][C@]12COC(=O)[C@]1([H])[C@H](C1=CC(OC)=C(O)C(OC)=C1)C1=CC3=C(OCO3)C=C1[C@H]2O[C@@H]1O[C@]2([H])CO[C@@H](C)O[C@@]2([H])[C@H](O)[C@H]1O
Độ tan chảy
236-251 °C
Độ hòa tan
Sparingly soluble
logP
0.60
logS
-2.8
pKa (strongest acidic)
9.33
pKa (Strongest Basic)
-3.7
PSA
160.83 Å2
Refractivity
139.02 m3·mol-1
Polarizability
58.77 Å3
Rotatable Bond Count
5
H Bond Acceptor Count
12
H Bond Donor Count
3
Physiological Charge
0
Number of Rings
7
Bioavailability
0
Dược Lực Học : Etoposide is an antineoplastic agent and an epipodophyllotoxin (a semisynthetic derivative of the podophyllotoxins). It inhibits DNA topoisomerase II, thereby ultimately inhibiting DNA synthesis. Etoposide is cell cycle dependent and phase specific, affecting mainly the S and G2 phases. Two different dose-dependent responses are seen. At high concentrations (10 µg/mL or more), lysis of cells entering mitosis is observed. At low concentrations (0.3 to 10 µg/mL), cells are inhibited from entering prophase. It does not interfere with microtubular assembly. The predominant macromolecular effect of etoposide appears to be the induction of DNA strand breaks by an interaction with DNA-topoisomerase II or the formation of free radicals.
Cơ Chế Tác Dụng : A semisynthetic derivative of podophyllotoxin that exhibits antitumor activity. Etoposide inhibits DNA synthesis by forming a complex with topoisomerase II and DNA. This complex induces breaks in double stranded DNA and prevents repair by topoisomerase II binding. Accumulated breaks in DNA prevent entry into the mitotic phase of cell division, and lead to cell death. Etoposide acts primarily in the G2 and S phases of the cell cycle. [PubChem] Etoposide inhibits DNA topoisomerase II, thereby inhibiting DNA re-ligation. This causes critical errors in DNA synthesis at the premitotic stage of cell division and can lead to apoptosis of the cancer cell. Etoposide is cell cycle dependent and phase specific, affecting mainly the S and G2 phases of cell division. Inhibition of the topoisomerase II alpha isoform results in the anti-tumour activity of etoposide. The drug is also capable of inhibiting the beta isoform but inhibition of this target is not associated with the anti-tumour activity. It is instead associated with the carcinogenic effect.
Dược Động Học :
▧ Absorption :
Absorbed well, time to peak plasma concentration is 1-1.5 hrs. Mean bioavailability is 50% (range of 25% - 75%). Cmax and AUC values for orally administered etoposide capsules display intra- and inter-subject variability. There is no evidence of first-pass effect for etoposide.
▧ Volume of Distribution :
The disposition of etoposide is a biphasic process with a distribution half-life of 1.5 hours. It does not cross into cerebrospinal fluid well. Volume of distribution, steady state = 18 - 29 L.
▧ Protein binding :
97% protein bound.
▧ Metabolism :
Primarily hepatic (through O-demethylation via the CYP450 3A4 isoenzyme pathway) with 40% excreted unchanged in the urine. Etoposide also undergoes glutathione and glucuronide conjugation which are catalyzed by GSTT1/GSTP1 and UGT1A1, respectively. Prostaglandin synthases are also responsible for the conversion of etoposide to O-demethylated metabolites (quinone).
▧ Route of Elimination :
Etoposide is cleared by both renal and nonrenal processes, i.e., metabolism and biliary excretion. Glucuronide and/or sulfate conjugates of etoposide are also excreted in human urine. Biliary excretion of unchanged drug and/or metabolites is an important route of etoposide elimination as fecal recovery of radioactivity is 44% of the intravenous dose. 56% of the dose was in the urine, 45% of which was excreted as etoposide.
▧ Half Life :
4-11 hours
▧ Clearance :
* Total body clearance = 33 - 48 mL/min [IV administration, adults] * Mean renal clearance = 7 - 10 mL/min/m^2
Độc Tính : Side effects include alopecia, constipation, diarrhea, nausea and vomiting and secondary malignancies (leukemia).
Chỉ Định : For use in combination with other chemotherapeutic agents in the treatment of refractory testicular tumors and as first line treatment in patients with small cell lung cancer. Also used to treat other malignancies such as lymphoma, non-lymphocytic leukemia, and glioblastoma multiforme.
Tương Tác Thuốc :
  • Aprepitant Aprepitant may change levels of the chemotherapy agent, etoposide.
  • Cyclosporine Cyclosporine may increase the therapeutic and adverse effects of etoposide.
  • Quinupristin This combination presents an increased risk of toxicity
  • Telithromycin Telithromycin may reduce clearance of Etoposide. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Etoposide if Telithromycin is initiated, discontinued or dose changed.
  • Trastuzumab Trastuzumab may increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events.
  • Voriconazole Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of etoposide by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of etoposide if voriconazole is initiated, discontinued or dose changed.
Liều Lượng & Cách Dùng : Capsule - Oral - 50 mg
Injection, solution - Intravenous - 20 mg/mL
Dữ Kiện Thương Mại
Giá thị trường
Nhà Sản Xuất
Đóng gói
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB00773
PubChem Compound
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=36462
PubChem Substance
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=46505434
KEGG Compound
http://www.genome.jp/dbget-bin/www_bget?cpd:C01576
KEGG Drug
http://www.genome.jp/dbget-bin/www_bget?drug:D00125
ChemSpider
http://www.chemspider.com/Chemical-Structure.33510.html
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/0378-3266-94
PharmGKB
http://www.pharmgkb.org/drug/PA449552
Wikipedia
http://en.wikipedia.org/wiki/Etoposide
RxList
http://www.rxlist.com/cgi/generic2/etopophos.htm
Drugs.com
http://www.drugs.com/cdi/etoposide.html
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