Tìm theo
Aprepitant
Các tên gọi khác (4 ) :
  • 3-(((2R,3S)-3-(P-Fluorophenyl)-2-(((alphar)-alpha-methyl-3,5-bis(trifluoromethyl)benzyl)oxy)morpholino)methyl)-delta(2)-1,2,4-triazolin-5-one
  • Aprepitant
  • Aprépitant
  • Aprepitantum
Thuốc Gốc
Small Molecule
CAS: 170729-80-3
ATC: A04AD12
ĐG : Merck & Co. , http://www.merck.com
CTHH: C23H21F7N4O3
PTK: 534.4267
Aprepitant, an antiemetic, is 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).
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C23H21F7N4O3
Phân tử khối
534.4267
Monoisotopic mass
534.150187993
InChI
InChI=1S/C23H21F7N4O3/c1-12(14-8-15(22(25,26)27)10-16(9-14)23(28,29)30)37-20-19(13-2-4-17(24)5-3-13)34(6-7-36-20)11-18-31-21(35)33-32-18/h2-5,8-10,12,19-20H,6-7,11H2,1H3,(H2,31,32,33,35)/t12-,19+,20-/m1/s1
InChI Key
InChIKey=ATALOFNDEOCMKK-OITMNORJSA-N
IUPAC Name
3-{[(2R,3S)-2-[(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy]-3-(4-fluorophenyl)morpholin-4-yl]methyl}-4,5-dihydro-1H-1,2,4-triazol-5-one
Traditional IUPAC Name
aprepitant
SMILES
C[C@@H](O[C@H]1OCCN(CC2=NNC(=O)N2)[C@H]1C1=CC=C(F)C=C1)C1=CC(=CC(=C1)C(F)(F)F)C(F)(F)F
Độ hòa tan
Practically insoluble
logP
4.5
logS
-4.4
pKa (strongest acidic)
9.65
pKa (Strongest Basic)
3.51
PSA
75.19 Å2
Refractivity
116.93 m3·mol-1
Polarizability
45.56 Å3
Rotatable Bond Count
8
H Bond Acceptor Count
5
H Bond Donor Count
2
Physiological Charge
0
Number of Rings
4
Bioavailability
0
MDDR-Like Rule
true
Dược Lực Học : Aprepitant, an antiemetic, is 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 : Aprepitant, an antiemetic, is 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). 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.
Dược Động Học :
▧ Absorption :
The mean absolute oral bioavailability of aprepitant is approximately 60 to 65%.
▧ Volume of Distribution :
* 70 L
▧ 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
▧ Clearance :
* Apparent plasma cl=62-90 mL/min
Chỉ Định : For the prevention of nausea and vomiting associated with highly emetogenic cancer chemotherapy, including high-dose cisplatin (in combination with other antiemetic agents).
Tương Tác Thuốc :
  • Acenocoumarol Aprepitant may decrease the anticoagulant effect of acenocoumarol by decreasing its serum concentration.
  • Alprazolam Aprepitant may increase the effect and toxicity of the benzodiazepine, alprazolam.
  • Anisindione Aprepitant may decrease the anticoagulant effect of anisindione by decreasing its serum concentration.
  • Astemizole Increased risk of cardiotoxicity and arrhythmias
  • Carbamazepine The CYP3A4 inducer, carbamazepine, may decrease the effect of aprepitant.
  • Cisapride Increased risk of cardiotoxicity and arrhythmias
  • Clarithromycin The CYP3A4 inhibitor, clarithromycin, may increase the effect and toxicity of aprepitant.
  • Corticotropin Aprepitant may increase the serum concentration of Corticosteroids (Systemic). Monitor for increased effects of systemic corticosteroids when coadmininistered with aprepitant; corticosteroid dose reduction may be necessary. The manufacturer of fosaprepitant (a prodrug of aprepitant) 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. 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.
  • Dexamethasone Aprepitant may increase the effect and toxicity of dexamethasone.
  • Dicoumarol Aprepitant may decrease the anticoagulant effect of dicumarol by decreasing its serum concentration.
  • Diltiazem This CYP3A4 inhibitor increases the effect and toxicity of aprepitant
  • Docetaxel Aprepitant may change levels of the chemotherapy agent, docetaxel.
  • Erythromycin Erythromycin, a moderate CYP3A4 inhibitor, may increase the effect and toxicity of aprepitant.
  • Ethinyl Estradiol Aprepitant could decrease the effect of the oral contraceptive
  • Ethotoin The CYP3A4 inducer, ethotoin, may decrease the effect of aprepitant.
  • Etoposide Aprepitant may change levels of the chemotherapy agent, etoposide.
  • Fosphenytoin The CYP3A4 inducer, fosphenytoin, may decrease the effect of aprepitant.
  • Ifosfamide Aprepitant may change levels of the chemotherapy agent, ifosfamide.
  • Imatinib Aprepitant may change levels of the chemotherapy agent, imatinib.
  • Irinotecan Aprepitant may change levels of the chemotherapy agent, irinotecan.
  • Itraconazole This CYP3A4 inhibitor, itraconazole, may increase the effect and toxicity of aprepitant.
  • Ketoconazole This CYP3A4 inhibitor increases the effect and toxicity of aprepitant
  • Mephenytoin The CYP3A4 inducer, mephenytoin, may decrease the effect of aprepitant.
  • Mestranol Aprepitant could decrease the effect of the oral contraceptive
  • Methylprednisolone Increases the effect and toxicity of methylprednisolone
  • Midazolam Aprepitant may increase the effect and toxicity of the benzodiazepine, midazolam.
  • Nefazodone This CYP3A4 inhibitor increases the effect and toxicity of aprepitant
  • Nelfinavir This CYP3A4 inhibitor increases the effect and toxicity of aprepitant
  • Paclitaxel Aprepitant may change levels of the chemotherapy agent, paclitaxel.
  • Phenytoin The CYP3A4 inducer, phenytoin, may decrease the effect of aprepitant.
  • Pimozide Increased risk of cardiotoxicity and arrhythmias
  • Rifampicin The CYP3A4 inducer, rifampin, may decrease the effect of aprepitant.
  • Ritonavir This CYP3A4 inhibitor increases the effect and toxicity of aprepitant
  • Tamsulosin Aprepitant, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Aprepitant is initiated, discontinued, or dose changed.
  • Telithromycin Telithromycin may reduce clearance of Aprepitant. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Aprepitant if Telithromycin is initiated, discontinued or dose changed.
  • Terfenadine Increased risk of cardiotoxicity and arrhythmias
  • Tolterodine Aprepitant may decrease the metabolism and clearance of Tolterodine. Adjust Tolterodine dose and monitor for efficacy and toxicity.
  • Tramadol Aprepitant may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance.
  • Trazodone The CYP3A4 inhibitor, Aprepitant, may increase Trazodone efficacy/toxicity by decreasing Trazodone metabolism and clearance. Monitor for changes in Trazodone efficacy/toxicity if Aprepitant is initiated, discontinued or dose changed.
  • Triazolam Aprepitant may increase the effect and toxicity of the benzodiazepine, triazolam.
  • Troleandomycin This CYP3A4 inhibitor increases the effect and toxicity of aprepitant
  • Vinblastine Aprepitant may change levels of the chemotherapy agent, vinblastine.
  • Vincristine Aprepitant may change levels of the chemotherapy agent, vincristine.
  • Vinorelbine Aprepitant may change levels of the chemotherapy agent, vinorelbine.
  • Voriconazole Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of aprepitant by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of aprepitant if voriconazole is initiated, discontinued or dose changed.
  • Warfarin Aprepitant may decrease the anticoagulant effect of warfarin by decreasing its serum concentration.
Liều Lượng & Cách Dùng : Capsule - Oral
Dữ Kiện Thương Mại
Giá thị trường
Nhà Sản Xuất
  • Công ty : Glenmark
    Sản phẩm biệt dược : Aprecap
  • Công ty : Merck & Co.
    Sản phẩm biệt dược : Emend
Đóng gói
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB00673
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/0006-0461-02
PharmGKB
http://www.pharmgkb.org/drug/PA164747039
Wikipedia
http://en.wikipedia.org/wiki/Aprepitant
RxList
http://www.rxlist.com/cgi/generic3/emend.htm
Drugs.com
http://www.drugs.com/cdi/aprepitant.html
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