药品详细

Aprepitant(阿瑞)

基本信息
剂型规格
适应症
药理
临床
理化性质
相互作用
文档
专利
Pathway
文献
序列

化学结构式图

中文名

阿瑞

英文名

Aprepitant

分子式

C₂₃H₂₁F₇N₄O₃

化学名

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

分子量

Average: 534.4267
Monoisotopic: 534.150187993

CAS号

170729-80-3

ATC分类

A04A 未知

药物类型

small molecule

阶段

approved

商品名

同义名

基本介绍

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).

生产厂家

Merck and co inc

封装厂家

参考

Synthesis Reference	Not Available
General Reference	Not Available

剂型

规格

化合物类型

Type	small molecule

Classes

Not Available

Substructures

Not Available

适应症

药理

Indication

For the prevention of nausea and vomiting associated with highly emetogenic cancer chemotherapy, including high-dose cisplatin (in combination with other antiemetic agents).

Pharmacodynamics

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).

Mechanism of action

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.

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.

Important The metabolism module of DrugBank is currently in beta. Questions or suggestions? Please contact us.

Substrate	Enzymes	Product
Aprepitant	Cytochrome P450 3A4	(2S,3R)-2-[(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy]-3-(4-fluorophenyl)morpholine	Details
Aprepitant	Cytochrome P450 3A4 Cytochrome P450 1A2 Cytochrome P450 2C19	5-({[(1R)-1-(4-fluorophenyl)-2-hydroxyethyl]amino}methyl)-2,3-dihydro-1H-1,2,4-triazol-3-one	Details
Aprepitant	Cytochrome P450 3A4 Cytochrome P450 1A2 Cytochrome P450 2C19	(2R)-2-(4-fluorophenyl)-2-{[(5-oxo-2,5-dihydro-1H-1,2,4-triazol-3-yl)methyl]amino}acetic acid	Details

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

Toxicity

Not Available

Affected organisms

Humans and other mammals

Pathways

Not Available

理化性质

Properties

State

solid

Experimental Properties

Property	Value	Source
water solubility	Practically insoluble	Not Available
logP	4.5	Not Available

Predicted Properties

Property	Value	Source
water solubility	1.94e-02 g/l	ALOGPS
logP	2.44	ALOGPS
logP	5.22	ChemAxon
logS	-4.4	ALOGPS
pKa (strongest acidic)	9.65	ChemAxon
pKa (strongest basic)	3.51	ChemAxon
physiological charge	0	ChemAxon
hydrogen acceptor count	5	ChemAxon
hydrogen donor count	2	ChemAxon
polar surface area	75.19	ChemAxon
rotatable bond count	8	ChemAxon
refractivity	116.93	ChemAxon
polarizability	45.56	ChemAxon

药物相互作用

Drug	Interaction
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.
Dicumarol	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
Rifampin	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.

食物相互作用

Take without regard to meals.

返回 | 收藏