Tìm theo
Abiraterone
Các tên gọi khác (2) :
  • (3beta)-17-(Pyridin-3-yl)androsta-5,16-dien-3-ol
  • 17-(3-Pyridyl)androsta-5,16-dien-3beta-ol
Thuốc Gốc
Small Molecule
CAS: 154229-19-3
ATC: L02BX03
CTHH: C24H31NO
PTK: 349.509
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.
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C24H31NO
Phân tử khối
349.509
Monoisotopic mass
349.240564619
InChI
InChI=1S/C24H31NO/c1-23-11-9-18(26)14-17(23)5-6-19-21-8-7-20(16-4-3-13-25-15-16)24(21,2)12-10-22(19)23/h3-5,7,13,15,18-19,21-22,26H,6,8-12,14H2,1-2H3/t18-,19-,21-,22-,23-,24+/m0/s1
InChI Key
InChIKey=GZOSMCIZMLWJML-VJLLXTKPSA-N
IUPAC Name
(1S,2R,5S,10R,11S,15S)-2,15-dimethyl-14-(pyridin-3-yl)tetracyclo[8.7.0.0²,⁷.0¹¹,¹⁵]heptadeca-7,13-dien-5-ol
Traditional IUPAC Name
abiraterone
SMILES
[H][C@@]12CC=C(C3=CC=CN=C3)[C@@]1(C)CC[C@@]1([H])[C@@]2([H])CC=C2C[C@@H](O)CC[C@]12C
Độ hòa tan
3.05e-03 g/l
logP
3.97
logS
-5.1
pKa (strongest acidic)
18.2
pKa (Strongest Basic)
4.81
PSA
33.12 Å2
Refractivity
107.3 m3·mol-1
Polarizability
42.04 Å3
Rotatable Bond Count
1
H Bond Acceptor Count
2
H Bond Donor Count
1
Physiological Charge
0
Number of Rings
5
Bioavailability
1
Rule of Five
true
Ghose Filter
true
Dược Lực Học : 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.
Cơ Chế Tác Dụng : 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. 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.
Dược Động Học :
▧ 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.
▧ Route of Elimination :
Excreted via feces (~88%) and urine (~5%)
▧ Half Life :
Terminal elimination half-life = 5-14 hours
Độc Tính : 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.
Chỉ Định : Used in combination with prednisone for the treatment of metastatic, castration-resistant prostate cancer.
Tương Tác Thuốc :
  • 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.
  • Rifampicin 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.
Liều Lượng & Cách Dùng : Tablet - Oral - 250 mg
Dữ Kiện Thương Mại
Nhà Sản Xuất
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB05812
KEGG Drug
http://www.genome.jp/dbget-bin/www_bget?drug:D09701
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/57894-150-12
Wikipedia
http://en.wikipedia.org/wiki/Abiraterone
RxList
http://www.rxlist.com/zytiga-drug.htm
Drugs.com
http://www.drugs.com/mtm/abiraterone.html
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