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药品详细

Abiraterone(阿比特龙)

化学结构式图
中文名
阿比特龙
英文名
Abiraterone
分子式
C26H33NO2
化学名
(2R,5S,15S)-2,15-dimethyl-14-(pyridin-3-yl)tetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadeca-7,13-dien-5-yl acetate
分子量
Average: 391.5457
Monoisotopic: 391.251129305
CAS号
154229-19-3
ATC分类
L02B 未知
药物类型
small molecule
阶段
approved
商品名
同义名
基本介绍

Abiraterone is a derivative of steroidal progesterone and is an innovative drug that offers clinical benefit to patients with hormone refractory prostate cancer. Abiraterone is administered as an acetate salt prodrug because it has a higher bioavailability and less susceptible to hydrolysis than abiraterone itself. FDA approved on April 28, 2011.

生产厂家
    封装厂家
    参考
    Synthesis Reference Not Available
    General Reference
    1. O’Donnell A, Judson I, Dowsett M, Raynaud F, Dearnaley D, Mason M, Harland S, Robbins A, Halbert G, Nutley B, Jarman M: Hormonal impact of the 17alpha-hydroxylase/C(17,20)-lyase inhibitor abiraterone acetate (CB7630) in patients with prostate cancer. Br J Cancer. 2004 Jun 14;90(12):2317-25. Pubmed
    2. Ryan CJ, Cheng ML: Abiraterone acetate for the treatment of prostate cancer. Expert Opin Pharmacother. 2013 Jan;14(1):91-6. doi: 10.1517/14656566.2013.745852. Epub 2012 Nov 30. Pubmed
    剂型
    规格
    化合物类型
    Type small molecule
    Classes Not Available
    Substructures Not Available
    适应症
    药理
    Indication Used in combination with prednisone for the treatment of metastatic, castration-resistant prostate cancer.
    Pharmacodynamics Abiraterone is associated with decreases in PSA levels, tumor shrinkage (as evaluated by RECIST criteria), radiographic regression of bone metastases and improvement in pain. Levels of adrenocorticotropic hormones increased up to 6-fold but this can be suppressed by dexamethasone.
    Mechanism of action Abiraterone is an orally active inhibitor of the steroidal enzyme CYP17A1 (17 alpha-hydroxylase/C17,20 lyase). It inhibits CYP17A1 in a selective and irreversible manner via covalent binding mechanism. CYP17A1 is an enzyme that catalyzes the biosynthesis of androgen and is highly expressed in testicular, adrenal, and prostatic tumor tissue. More specifically, abiraterone inhibits the conversion of 17-hydroxyprognenolone to dehydroepiandrosterone (DHEA) by the enzyme CYP17A1 to decrease serum levels of testosterone and other androgens.
    Absorption Abiraterone itself is poorly absorbed and is susceptible to hydrolysis by esterases. The salt form, abiraterone acetate, is a prodrug which has a much higher oral bioavailability and is also esterase resistant. Peak drug concentrations of abiraterone were reached in 1.5 - 4 hours. Abiraterone acetate was rapidly and completely deacetylated into abiraterone-the parent salt form was not detectable in early pharmacokinetic studies. Food and high fat meals increases absorption 4.4-fold.
    Volume of distribution

    Vdss= 19,669 ± 13,358 L
    Protein binding >99% protein bound to alpha-1-acid glycoprotein and albumin.
    Metabolism
    Abiraterone acetate is hydrolyzed into active metabolite abiraterone via esterases. CYP3A4 and SULT2A1 further metabolizes abiraterone into two inactive metabolites called abiraterone sulfate and N-oxide abiraterone sulfate.

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

    Substrate Enzymes Product
    Abiraterone
      		abiraterone sulfate Details
      Abiraterone
        		N-oxide abiraterone sulfate Details
        Route of elimination Excreted via feces (~88%) and urine (~5%)
        Half life Terminal elimination half-life = 5-14 hours
        Clearance Not Available
        Toxicity Toxicity is related to the blockade of 17α-hydroxylase activity. Blockade results in the accumulation of upstream mineralocorticoids like 11-deoxycorticosterone leading to secondary hyperaldosteronism. Signs of hydroaldosteronism include fluid retention and hypokalemia. Mineralocorticoid receptor antagonists may be used to treat signs and symptoms.
        Affected organisms
        • Humans and other mammals
        Pathways Not Available
        理化性质
        Properties
        State solid
        Experimental Properties Not Available
        Predicted Properties
        Property Value Source
        water solubility 1.01e-03 g/l ALOGPS
        logP 5.63 ALOGPS
        logP 4.41 ChemAxon
        logS -5.6 ALOGPS
        pKa (strongest basic) 4.81 ChemAxon
        physiological charge 0 ChemAxon
        hydrogen acceptor count 2 ChemAxon
        hydrogen donor count 0 ChemAxon
        polar surface area 39.19 ChemAxon
        rotatable bond count 3 ChemAxon
        refractivity 116.45 ChemAxon
        polarizability 46.58 ChemAxon
        药物相互作用
        Drug Interaction
        Atazanavir Strong CYP3A4 inhibitors may increase levels of abiraterone. Monitor concomitant therapy closely.
        Bosutinib Abiraterone increases levels by P-glycoprotein (MDR1) efflux transporter. Consider alternate therapy.
        Carbamazepine Strong CYP3A4 inducers may decrease levels of abiraterone. Monitor concomitant therapy closely.
        Clarithromycin Strong CYP3A4 inhibitors may increase levels of abiraterone. Monitor concomitant therapy closely.
        Dextromethorphan Abiraterone increases levels by affecting CYP2D6 metabolism. Interaction is significant so monitor closely.
        Indinavir Strong CYP3A4 inhibitors may increase levels of abiraterone. Monitor concomitant therapy closely.
        Itraconazole Strong CYP3A4 inhibitors may increase levels of abiraterone. Monitor concomitant therapy closely.
        Ketoconazole Strong CYP3A4 inhibitors may increase levels of abiraterone. Monitor concomitant therapy closely.
        Nefazodone Strong CYP3A4 inhibitors may increase levels of abiraterone. Monitor concomitant therapy closely.
        Nelfinavir Strong CYP3A4 inhibitors may increase levels of abiraterone. Monitor concomitant therapy closely.
        Phenobarbital Strong CYP3A4 inducers may decrease levels of abiraterone. Monitor concomitant therapy closely.
        Phenytoin Strong CYP3A4 inducers may decrease levels of abiraterone. Monitor concomitant therapy closely.
        Rifabutin Strong CYP3A4 inducers may decrease levels of abiraterone. Monitor concomitant therapy closely.
        Rifampin Strong CYP3A4 inducers may decrease levels of abiraterone. Monitor concomitant therapy closely.
        Rifapentine Strong CYP3A4 inducers may decrease levels of abiraterone. Monitor concomitant therapy closely.
        Ritonavir Strong CYP3A4 inhibitors may increase levels of abiraterone. Monitor concomitant therapy closely.
        Saquinavir Strong CYP3A4 inhibitors may increase levels of abiraterone. Monitor concomitant therapy closely.
        Telithromycin Strong CYP3A4 inhibitors may increase levels of abiraterone. Monitor concomitant therapy closely.
        Thioridazine Abiraterone increases levels by affecting CYP2D6 metabolism. Interaction is significant so monitor closely.
        Voriconazole Strong CYP3A4 inhibitors may increase levels of abiraterone. Monitor concomitant therapy closely.
        食物相互作用
        • Food and high fat meals increases the drug exposure 4.4-fold. It is suggested that abiraterone is taken on an empty stomach.

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