Tìm theo
Fosaprepitant
Các tên gọi khác (3) :
  • Fosaprepitantum
  • L-758,298
  • L-758298
Thuốc Gốc
Small Molecule
CAS: 172673-20-0
CTHH: C23H22F7N4O6P
PTK: 614.4066
Fosaprepitant is an intravenously administered antiemetic drug. It is a prodrug of Aprepitant. It aids in the prevention of acute and delayed nausea and vomiting associated with chemotherapy treatment.
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C23H22F7N4O6P
Phân tử khối
614.4066
Monoisotopic mass
614.116518403
InChI
InChI=1S/C23H22F7N4O6P/c1-12(14-8-15(22(25,26)27)10-16(9-14)23(28,29)30)40-20-19(13-2-4-17(24)5-3-13)33(6-7-39-20)11-18-31-21(35)34(32-18)41(36,37)38/h2-5,8-10,12,19-20H,6-7,11H2,1H3,(H,31,32,35)(H2,36,37,38)/t12-,19+,20-/m1/s1
InChI Key
InChIKey=BARDROPHSZEBKC-OITMNORJSA-N
IUPAC Name
(3-{[(2R,3S)-2-[(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy]-3-(4-fluorophenyl)morpholin-4-yl]methyl}-5-oxo-2,5-dihydro-1H-1,2,4-triazol-1-yl)phosphonic acid
Traditional IUPAC Name
3-{[(2R,3S)-2-[(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy]-3-(4-fluorophenyl)morpholin-4-yl]methyl}-5-oxo-2H-1,2,4-triazol-1-ylphosphonic acid
SMILES
C[C@@H](O[C@H]1OCCN(CC2=NC(=O)N(N2)P(O)(O)=O)[C@H]1C1=CC=C(F)C=C1)C1=CC(=CC(=C1)C(F)(F)F)C(F)(F)F
Độ hòa tan
6.32e-03 g/l
logP
2.4
logS
-5
pKa (strongest acidic)
1.02
pKa (Strongest Basic)
5.69
PSA
123.93 Å2
Refractivity
138.63 m3·mol-1
Polarizability
49.92 Å3
Rotatable Bond Count
9
H Bond Acceptor Count
9
H Bond Donor Count
3
Physiological Charge
-2
Number of Rings
4
Bioavailability
1
MDDR-Like Rule
true
Dược Lực Học : Fosaprepitant is a prodrug of Aprepitant. Once biologically activated, the drug acts as a substance P/neurokinin 1 (NK1) receptor antagonist which, in combination with other antiemetic agents, is indicated for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy. Aprepitant is a selective high-affinity antagonist of human substance P/neurokinin 1 (NK1) receptors. Aprepitant has little or no affinity for serotonin (5-HT3), dopamine, and corticosteroid receptors, the targets of existing therapies for chemotherapy-induced nausea and vomiting (CI NV).
Cơ Chế Tác Dụng : Fosaprepitant is an intravenously administered antiemetic drug. It is a prodrug of Aprepitant. It aids in the prevention of acute and delayed nausea and vomiting associated with chemotherapy treatment. Aprepitant has been shown in animal models to inhibit emesis induced by cytotoxic chemotherapeutic agents, such as cisplatin, via central actions. Animal and human Positron Emission Tomography (PET) studies with Aprepitant have shown that it crosses the blood brain barrier and occupies brain NK1 receptors. Animal and human studies show that Aprepitant augments the antiemetic activity of the 5-HT3-receptor antagonist ondansetron and the corticosteroid ethasone and inhibits both the acute and delayed phases of cisplatin induced emesis. In summary, the active form of fosaprepitant is as an NK1 antagonist which is because it blocks signals given off by NK1 receptors. This therefore decreases the likelihood of vomiting in patients experiencing.
Dược Động Học :

▧ Protein binding :
95% +
▧ Metabolism :
Aprepitant is metabolized primarily by CYP3A4 with minor metabolism by CYP1A2 and CYP2C19. Seven metabolites of aprepitant, which are only weakly active, have been identified in human plasma.
▧ Route of Elimination :
Aprepitant is eliminated primarily by metabolism; aprepitant is not renally excreted. Aprepitant is excreted in the milk of rats. It is not known whether this drug is excreted in human milk.
▧ Half Life :
9-13 hours
Chỉ Định : For the prevention of nausea and vomiting associated with highly emetogenic cancer chemotherapy.
Tương Tác Thuốc :
  • Corticotropin Fosaprepitant may increase the serum concentration of Corticosteroids (Systemic). The active metabolite aprepitant is likely responsible for this effect. The manufacturer of fosaprepitant states that oral dexamethasone doses should be reduced by 50% when coadministered with a fosaprepitant/aprepitant regimen to achieve dexamethasone concentrations similar to those achieved with dexamethasone alone.1 Dexamethasone doses used in clinical chemotherapy nausea/vomiting studies with aprepitant reflect this 50% decrease. Similarly, it is recommended that in order to achieve concentrations similar to those achieved with methylprednisolone alone, the intravenous methylprednisolone dose should be reduced by 25% and the oral methylprednisolone dose should be reduced by 50% when given together with a fosaprepitant/aprepitant regimen. Monitor for increased effects of systemic corticosteroids when coadmininistered with fosaprepitant or aprepitant.
Dữ Kiện Thương Mại
Nhà Sản Xuất
  • Công ty : Merck Frosst
    Sản phẩm biệt dược : Emend
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB06717
PubChem Compound
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=219090
PubChem Substance
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=99443269
KEGG Drug
http://www.genome.jp/dbget-bin/www_bget?drug:D06597
PharmGKB
http://www.pharmgkb.org/drug/PA165958390
Wikipedia
http://en.wikipedia.org/wiki/Fosaprepitant
... loading
... loading