Tìm theo
Irinotecan
Các tên gọi khác (2) :
  • Biotecan
  • Camptothecin-11
Thuốc chống ung thư và tác động vào hệ thống miễn dịch
Thuốc Gốc
Small Molecule
CAS: 100286-90-6
ATC: L01XX19
ĐG : Actavis Group , http://www.actavis.com
CTHH: C33H38N4O6
PTK: 586.678
Irinotecan is an antineoplastic enzyme inhibitor primarily used in the treatment of colorectal cancer. It is a derivative of camptothecin that inhibits the action of topoisomerase I. Irinotecan prevents religation of the DNA strand by binding to topoisomerase I-DNA complex, and causes double-strand DNA breakage and cell death. It is a derivative of camptothecin.
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C33H38N4O6
Phân tử khối
586.678
Monoisotopic mass
586.279134968
InChI
InChI=1S/C33H38N4O6/c1-3-22-23-16-21(43-32(40)36-14-10-20(11-15-36)35-12-6-5-7-13-35)8-9-27(23)34-29-24(22)18-37-28(29)17-26-25(30(37)38)19-42-31(39)33(26,41)4-2/h8-9,16-17,20,41H,3-7,10-15,18-19H2,1-2H3/t33-/m0/s1
InChI Key
InChIKey=UWKQSNNFCGGAFS-XIFFEERXSA-N
IUPAC Name
(19S)-10,19-diethyl-19-hydroxy-14,18-dioxo-17-oxa-3,13-diazapentacyclo[11.8.0.0^{2,11}.0^{4,9}.0^{15,20}]henicosa-1(21),2(11),3,5,7,9,15(20)-heptaen-7-yl 4-(piperidin-1-yl)piperidine-1-carboxylate
Traditional IUPAC Name
irinotecan
SMILES
CCC1=C2CN3C(=CC4=C(COC(=O)[C@]4(O)CC)C3=O)C2=NC2=C1C=C(OC(=O)N1CCC(CC1)N1CCCCC1)C=C2
Độ tan chảy
222-223 °C
Độ hòa tan
Soluble
logP
3.2
logS
-3.7
pKa (strongest acidic)
11.71
pKa (Strongest Basic)
9.47
PSA
112.51 Å2
Refractivity
161.33 m3·mol-1
Polarizability
65.27 Å3
Rotatable Bond Count
5
H Bond Acceptor Count
6
H Bond Donor Count
1
Physiological Charge
1
Number of Rings
7
Bioavailability
1
Dược Lực Học : Irinotecan is an antineoplastic enzyme inhibitor primarily used in the treatment of colorectal cancer. Irinotecan is a semisynthetic derivative of camptothecin. Camptothecins interact specifically with topoisomerase I, an enzyme in the cell nucleus that regulates DNA topology and facilitates nuclear processes such as DNA replication, recombination, and repair. During these processes, topoisomerase I relieves torsional strain in DNA by inducing reversible single-strand breaks, allowing single DNA strands to pass through the break. The 3'-DNA terminus of the broken DNA strands bind covalently with the topoisomerase enzyme to form a catalytic intermediate called a cleavable complex. After the DNA is sufficiently relaxed and the strand passage reaction is complete, DNA topoisomerase reattaches the broken DNA strands to form the chemically unaltered topoisomers that allow transcription to proceed. Irinotecan and its active metabolite SN-38 bind to the topoisomerase I-DNA complex and prevent religation of these single-strand breaks. Current research suggests that the cytotoxicity of irinotecan is due to double-strand DNA damage produced during DNA synthesis when replication enzymes interact with the ternary complex formed by topoisomerase I, DNA, and either Irinotecan or SN-38. Mammalian cells cannot efficiently repair these double-strand breaks. The precise contribution of SN-38 to the activity of irinotecan in humans is not known. Irinotecan is cell cycle phase-specific (S-phase).
Cơ Chế Tác Dụng : Irinotecan is an antineoplastic enzyme inhibitor primarily used in the treatment of colorectal cancer. It is a derivative of camptothecin that inhibits the action of topoisomerase I. Irinotecan prevents religation of the DNA strand by binding to topoisomerase I-DNA complex, and causes double-strand DNA breakage and cell death. It is a derivative of camptothecin. Irinotecan inhibits the action of topoisomerase I. Irinotecan prevents religation of the DNA strand by binding to topoisomerase I-DNA complex. The formation of this ternary complex interferes with the moving replication fork, which induces replication arrest and lethal double-stranded breaks in DNA. As a result, DNA damage is not efficiently repaired and apoptosis (programmed cell death) occurs.
Dược Động Học :
▧ Absorption :
The maximum plasma concentration (Cmax) when a dose of 125 mg/m^2 is given to patients with solid tumours is 1660 ng/mL. The AUC (0-24) is 10,200 ng·h/mL. The Cmax when a dose of 340 mg/m^2 is given to patients with solid tumours is 3392 ng/mL. The AUC (0-24) is 20,604 ng·h/mL.
▧ Volume of Distribution :
The volume of distribution of terminal elimination phase is 110 L/m^2 when a dose of 125 mg/m^2 is given to patients with solid tumours. The volume of distribution of terminal elimination phase is 234 L/m^2 when a dose of 340 mg/m^2 is given to patients with solid tumours.
▧ Protein binding :
30%-68% protein bound, mainly to albumin.
▧ Metabolism :
Hepatic. The metabolic conversion of irinotecan to the active metabolite SN-38 is mediated by carboxylesterase enzymes and primarily occurs in the liver. SN-38 is subsequently conjugated predominantly by the enzyme UDP-glucuronosyl transferase 1A1 (UGT1A1) to form a glucuronide metabolite.
▧ Route of Elimination :
The cumulative biliary and urinary excretion of irinotecan and its metabolites (SN-38 and SN-38 glucuronide) over a period of 48 hours following administration of irinotecan in two patients ranged from approximately 25% (100 mg/m2) to 50% (300 mg/m2).
▧ Half Life :
The half life of irinotecan is about 6 - 12 hours. The terminal elimination half-life of the active metabolite, SN-38 is 10 - 20 hours.
▧ Clearance :
* 13.3 L/h/m^2 [Dose of 125 mg/m^2, patients with solid tumours] * 13.9 L/h/m^2 [Dose of 340 mg/m^2, patients with solid tumours]
Độc Tính : Gastrointestinal complications, such as nausea, vomiting, abdominal cramping, diarrhea, and infection.
Chỉ Định : For the treatment of metastatic colorectal cancer (first-line therapy when administered with 5-fluorouracil and leucovorin). Also used in combination with cisplatin for the treatment of extensive small cell lung cancer. Irinotecan is currently under investigation for the treatment of metastatic or recurrent cervical cancer.
Tương Tác Thuốc :
  • Aprepitant Aprepitant may change levels of the chemotherapy agent, irinotecan.
  • Atazanavir Increases levels/effect of irinotecan
  • Bevacizumab Monitor therapy due to increased adverse effects of irinotecan.
  • Fosphenytoin The hydantoin decreases the effect of irinotecan
  • Ketoconazole Ketoconazole increases the effect and toxicity of irinotecan
  • Pazopanib Irinotecan is an uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) substrate and serum concentrations may increase if administered concurrently with pazopanib, an UGT1A1 inhibitor.
  • Phenytoin The hydantoin decreases the effect of irinotecan
  • Regorafenib Regorafenib may increase levels of irinotecan, a UGT1A1 substrate.
  • Telithromycin Telithromycin may reduce clearance of Irinotecan. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Irinotecan if Telithromycin is initiated, discontinued or dose changed.
  • Thiotepa Thiotepa, a strong CYP2B6 inhibitor, may decrease the metabolism and clearance of Irinotecan, a CYP2B6 substrate. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of Irinotecan if Thiotepa 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 irinotecan by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of irinotecan if voriconazole is initiated, discontinued or dose changed.
Liều Lượng & Cách Dùng : Injection, solution - Intravenous - 40 mg/2 mL; 100 mg/5 mL; 300 mg/15 mL
Dữ Kiện Thương Mại
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Nhà Sản Xuất
Đóng gói
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB00762
PubChem Compound
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=60838
PubChem Substance
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=46505871
KEGG Compound
http://www.genome.jp/dbget-bin/www_bget?cpd:C16641
KEGG Drug
http://www.genome.jp/dbget-bin/www_bget?drug:D08086
ChemSpider
http://www.chemspider.com/Chemical-Structure.54825.html
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/0703-4432-11
PharmGKB
http://www.pharmgkb.org/drug/PA450085
Wikipedia
http://en.wikipedia.org/wiki/Irinotecan
RxList
http://www.rxlist.com/cgi/generic2/irinot.htm
Drugs.com
http://www.drugs.com/cdi/irinotecan.html
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