Abiraterone

349.51

349.51

1308068-626-2

G819A456D0

749226

C77333

L02BX03|L - Antineoplastic and immunomodulating agents

2933399090

33.1

5.70

white solid

1.14g/cm3

227-228 °C @ Solvent: Toluene

500.2±50.0 °C at 760 mmHg

256.3±30.1 °C

1.606

7.99E-11mmHg at 25°C

P201, P202, P260, P281, P308+P313, P314, P405, P501

H361

|Danger|H360 (80%): May damage fertility or the unborn child [Danger Reproductive toxicity]|P201, P202, P260, P273, P281, P308+P313, P314, P391, P405, and P501|Aggregated GHS information provided by 5 companies from 2 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

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.

Serum aminotransferase elevations occur in up to 13% of patients treated with abiraterone compared with 1% to 8% receiving placebo, but the abnormalities are generally mild, transient and not associated with symptoms or jaundice. ALT elevations above 5 times the upper limit of normal (ULN) occur in 6% of abiraterone treated vs

>99% protein bound to alpha-1-acid glycoprotein and albumin.

Used in combination with prednisone for the treatment of metastatic, castration-resistant prostate cancer.|FDA Label|Zytiga is indicated with prednisone or prednisolone for:the treatment of metastatic castration resistant prostate cancer in adult men who are asymptomatic or mildly symptomatic after failure of androgen deprivation therapy in whom chemotherapy is not yet clinically indicatedthe treatment of metastatic castration resistant prostate cancer in adult men whose disease has progressed on or after a docetaxel based chemotherapy regimen.|Abiraterone Accord is indicated with prednisone or prednisolone for:the treatment of newly diagnosed high risk metastatic hormone sensitive prostate cancer (mHSPC) in adult men in combination with androgen deprivation therapy (ADT)the treatment of metastatic castration resistant prostate cancer (mCRPC) in adult men who are asymptomatic or mildly symptomatic after failure of androgen deprivation therapy in whom chemotherapy is not yet clinically indicatedthe treatment of mCRPC in adult men whose disease has progressed on or after a docetaxel based chemotherapy regimen.

Abiraterone is an antiandrogen used to treat metastatic, castration-resistant prostate cancer. Abiraterone is associated with a not uncommon rate of serum enzyme elevation during therapy, but has not been clearly linked to cases of clinically apparent liver injury with jaundice.

Antineoplastic Agents

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.

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.|Excreted via feces (~88%) and urine (~5%)|Vdss= 19,669 ± 13,358 L

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.|Abiraterone has known human metabolites that include abiraterone sulfate.

Terminal elimination half-life = 5-14 hours

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.

17-(3-pyridyl)androsta-5,16-dien-3beta-ol

Human drugs -> Zytiga -> EMA Drug Category|Endocrine therapy -> Human pharmacotherapeutic group|Human drugs -> Abiraterone Accord -> EMA Drug Category