Tìm theo
Palonosetron
Các tên gọi khác (7 ) :
  • (3aS)-2-[(3S)-1-azabicyclo[2.2.2]oct-3-yl]-2,3,3a, 4,5,6-hexahydro-1H-benz[de]isoquinolin-1-one
  • (3aS)-2,3,3a,4,5,6-hexahydro-2-[(3S)-3-quinuclidinyl]-1H-benz[de]isoquinolin-1-one
  • Palonosetron
  • Palonosétron
  • Palonosetrón
  • Palonosetronum
  • SID50111798
Thuốc Gốc
Small Molecule
CAS: 119904-90-4
ATC: A04AA05
ĐG : Cardinal Health , http://www.cardinal.com
CTHH: C19H24N2O
PTK: 296.4067
Palonosetron (INN, trade name Aloxi) is a 5-HT3 antagonist used in the prevention and treatment of chemotherapy-induced nausea and vomiting (CINV). It is the most effective of the 5-HT3 antagonists in controlling delayed CINV nausea and vomiting that appear more than 24 hours after the first dose of a course of chemotherapy and is the only drug of its class approved for this use by the U.S. Food and Drug Administration. As of 2008, it is the most recent 5-HT3 antagonist to enter clinical use. [wikipedia]
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C19H24N2O
Phân tử khối
296.4067
Monoisotopic mass
296.1888634
InChI
InChI=1S/C19H24N2O/c22-19-16-6-2-4-14-3-1-5-15(18(14)16)11-21(19)17-12-20-9-7-13(17)8-10-20/h2,4,6,13,15,17H,1,3,5,7-12H2/t15-,17+/m0/s1
InChI Key
InChIKey=CPZBLNMUGSZIPR-DOTOQJQBSA-N
IUPAC Name
(5R)-3-[(3S)-1-azabicyclo[2.2.2]octan-3-yl]-3-azatricyclo[7.3.1.0^{5,13}]trideca-1(13),9,11-trien-2-one
Traditional IUPAC Name
(5R)-3-[(3S)-1-azabicyclo[2.2.2]octan-3-yl]-3-azatricyclo[7.3.1.0^{5,13}]trideca-1(13),9,11-trien-2-one
SMILES
[H][C@@]12CCCC3=C1C(=CC=C3)C(=O)N(C2)[C@@H]1CN2CCC1CC2
Độ hòa tan
4.64e-01 g/l
logP
2.7
logS
-2.8
pKa (Strongest Basic)
7.97
PSA
23.55 Å2
Refractivity
88.52 m3·mol-1
Polarizability
33.87 Å3
Rotatable Bond Count
1
H Bond Acceptor Count
2
H Bond Donor Count
0
Physiological Charge
1
Number of Rings
5
Bioavailability
1
Rule of Five
true
Ghose Filter
true
Dược Lực Học : Palonosetron is an antinauseant and antiemetic agent indicated for the prevention of nausea and vomiting associated with moderately-emetogenic cancer chemotherapy and for the prevention of postoperative nausea and vomiting. Palonosetron is a highly specific and selective serotonin 5-HT3 receptor antagonist that is pharmacologically related to other 5-HT3 receptor antagonists, but differs structurally. Palonosetron has a high affinity for 5-HT3 receptors, but has little to no affinity for other receptors. The serontonin 5-HT3 receptors are located on the nerve terminals of the vagus in the periphery, and centrally in the chemoreceptor trigger zone of the area postrema. It is suggested that chemotherapeutic agents release serotonin from the enterochromaffin cells of the small intestine by causing degenerative changes in the GI tract. The serotonin then stimulates the vagal and splanchnic nerve receptors that project to the medullary vomiting center, as well as the 5-HT3 receptors in the area postrema, thus initiating the vomiting reflex, causing nausea and vomiting.
Cơ Chế Tác Dụng : Palonosetron (INN, trade name Aloxi) is a 5-HT3 antagonist used in the prevention and treatment of chemotherapy-induced nausea and vomiting (CINV). It is the most effective of the 5-HT3 antagonists in controlling delayed CINV nausea and vomiting that appear more than 24 hours after the first dose of a course of chemotherapy and is the only drug of its class approved for this use by the U.S. Food and Drug Administration. As of 2008, it is the most recent 5-HT3 antagonist to enter clinical use. [wikipedia] Palonosetron is a selective serotonin 5-HT3 receptor antagonist. The antiemetic activity of the drug is brought about through the inhibition of 5-HT3 receptors present both centrally (medullary chemoreceptor zone) and peripherally (GI tract). This inhibition of 5-HT3 receptors in turn inhibits the visceral afferent stimulation of the vomiting center, likely indirectly at the level of the area postrema, as well as through direct inhibition of serotonin activity within the area postrema and the chemoreceptor trigger zone. Alternative mechanisms appear to be primarily responsible for delayed nausea and vomiting induced by emetogenic chemotherapy, since similar temporal relationships between between serotonin and emesis beyond the first day after a dose have not been established, and 5-HT3 receptor antagonists generally have not appeared to be effective alone in preventing or ameliorating delayed effects. It has been hypothesized that palonosetron's potency and long plasma half-life may contribute to its observed efficacy in preventing delayed nausea and vomiting caused by moderately emetogenic cancer chemotherapy.
Dược Động Học :
▧ Absorption :
Low oral bioavailability.
▧ Volume of Distribution :
* 8.3 ± 2.5 L/kg
▧ Protein binding :
62%
▧ Metabolism :
Hepatic (50%), primarily CYP2D6-mediated, although CYP3A4 and CYP1A2 are also involved.
▧ Route of Elimination :
After a single intravenous dose of 10 mcg/kg [14C]-palonosetron, approximately 80% of the dose was recovered within 144 hours in the urine
▧ Half Life :
Approximately 40 hours
▧ Clearance :
* 160 +/- 35 mL/h/kg
Độc Tính : A single intravenous dose of palonosetron at 30 mg/kg (947 and 474 times the human dose for rats and mice, respectively, based on body surface area) was lethal to rats and mice. The major signs of toxicity were convulsions, gasping, pallor, cyanosis and collapse.
Chỉ Định : For the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy, as well as prevention of acute nausea and vomiting associated with highly emetogenic cancer chemotherapy. Also used for the prevention of postoperative nausea and vomiting for up to 24 hours post operation.
Liều Lượng & Cách Dùng : Solution - Intravenous
Dữ Kiện Thương Mại
Giá thị trường
Nhà Sản Xuất
  • Công ty : Helsinn
    Sản phẩm biệt dược : Aloxi
  • Sản phẩm biệt dược : Jiouting
  • Công ty : Pfizer
    Sản phẩm biệt dược : Onicit
  • Công ty : Glenmark
    Sản phẩm biệt dược : Palnox
  • Công ty : Kalbe
    Sản phẩm biệt dược : Paloxi
  • Công ty : Dr. Reddy's
    Sản phẩm biệt dược : Palzen
  • Công ty : Themis Medicare
    Sản phẩm biệt dược : Themiset
  • Sản phẩm biệt dược : Zhiruo
Đóng gói
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB00377
PubChem Compound
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=148211
PubChem Substance
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=46508530
ChemSpider
http://www.chemspider.com/Chemical-Structure.130656.html
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/58063-797-25
PharmGKB
http://www.pharmgkb.org/drug/PA10352
Wikipedia
http://en.wikipedia.org/wiki/Palonosetron
RxList
http://www.rxlist.com/cgi/generic/aloxi.htm
Drugs.com
http://www.drugs.com/cdi/palonosetron.html
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