Description

Simple

An anti-tumor hormone therapy used for the treatment of certain types of prostate cancer.

Clinical

An antiandrogen used in the treatment of prostate cancer.

Overview

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.

Pharmacology

Indication

Used in combination with prednisone for the treatment of metastatic, castration-resistant prostate cancer.

Pharmacodynamic

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 testic... Read more

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 acetat... Read more

Protein binding

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

Volume of distribution

Vdss= 19,669 ± 13,358 L

Clearance

Information currently not available.

Half life

Terminal elimination half-life = 5-14 hours

Route of elimination

Excreted via feces (~88%) and urine (~5%)

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 an... Read more

Adverse Effects

Effect Regions Age Groups Incidences Evidence Type
Hypertriglyceridemia US
  • Kind: experimental
    • Percent: 62.5%
  • Kind: placebo
    • Percent: 53%
  • Clinical Trial
    Hyperglycemia US
  • Kind: experimental
    • Percent: 56.6%
  • Kind: placebo
    • Percent: 50.9%
  • Clinical Trial
    High alanine transaminase US
  • Kind: experimental
    • Percent: 41.9%
  • Kind: placebo
    • Percent: 29.1%
  • Clinical Trial
    Fatigue US
  • Kind: experimental
    • Percent: 39.1%
  • Kind: placebo
    • Percent: 34.3%
  • Clinical Trial
    Lymphopenia US
  • Kind: experimental
    • Percent: 38.2%
  • Kind: placebo
    • Percent: 31.7%
  • Clinical Trial
    High aspartate transaminase US
  • Kind: experimental
    • Percent: 37.3%
  • Kind: placebo
    • Percent: 28.7%
  • Clinical Trial
    High aspartate transaminase US
  • Kind: experimental
    • Percent: 30.6%
  • Kind: placebo
    • Percent: 36.3%
  • Clinical Trial
    Hypernatremia US
  • Kind: experimental
    • Percent: 32.8%
  • Kind: placebo
    • Percent: 25%
  • Clinical Trial
    Joint Discomfort US
  • Kind: experimental
    • Percent: 30.3%
  • Kind: placebo
    • Percent: 25.2%
  • Clinical Trial
    Joint swelling US
  • Kind: experimental
    • Percent: 30.3%
  • Kind: placebo
    • Percent: 25.2%
  • Clinical Trial
    Joint swelling US
  • Kind: experimental
    • Percent: 29.5%
  • Kind: placebo
    • Percent: 23.4%
  • Clinical Trial
    Joint Discomfort US
  • Kind: experimental
    • Percent: 29.5%
  • Kind: placebo
    • Percent: 23.4%
  • Clinical Trial
    Hypokalemia US
  • Kind: experimental
    • Percent: 28.3%
  • Kind: placebo
    • Percent: 19.8%
  • Clinical Trial
    Edema US
  • Kind: experimental
    • Percent: 26.7%
  • Kind: placebo
    • Percent: 18.3%
  • Clinical Trial
    Muscle discomfort US
  • Kind: experimental
    • Percent: 26.2%
  • Kind: placebo
    • Percent: 23.1%
  • Clinical Trial
    Edema US
  • Kind: experimental
    • Percent: 25.1%
  • Kind: placebo
    • Percent: 20.7%
  • Clinical Trial
    Hypophosphatemia US
  • Kind: experimental
    • Percent: 23.8%
  • Kind: placebo
    • Percent: 15.7%
  • Clinical Trial
    Constipation US
  • Kind: experimental
    • Percent: 23.1%
  • Kind: placebo
    • Percent: 19.1%
  • Clinical Trial
    Hot flush US
  • Kind: experimental
    • Percent: 22.3%
  • Kind: placebo
    • Percent: 18.1%
  • Clinical Trial
    Hypertension US
  • Kind: experimental
    • Percent: 21.6%
  • Kind: placebo
    • Percent: 13.1%
  • Clinical Trial
    Diarrhea US
  • Kind: experimental
    • Percent: 21.6%
  • Kind: placebo
    • Percent: 17.8%
  • Clinical Trial
    Hot flush US
  • Kind: experimental
    • Percent: 19%
  • Kind: placebo
    • Percent: 16.8%
  • Clinical Trial
    Diarrhea US
  • Kind: experimental
    • Percent: 17.6%
  • Kind: placebo
    • Percent: 13.5%
  • Clinical Trial
    Cough US
  • Kind: experimental
    • Percent: 17.3%
  • Kind: placebo
    • Percent: 13.5%
  • Clinical Trial
    Hypokalemia US
  • Kind: experimental
    • Percent: 17.2%
  • Kind: placebo
    • Percent: 10.2%
  • Clinical Trial
    Insomnia US
  • Kind: experimental
    • Percent: 13.5%
  • Kind: placebo
    • Percent: 11.3%
  • Clinical Trial
    Contusion US
  • Kind: experimental
    • Percent: 13.3%
  • Kind: placebo
    • Percent: 9.1%
  • Clinical Trial
    Upper Respiratory Tract Infection US
  • Kind: experimental
    • Percent: 12.7%
  • Kind: placebo
    • Percent: 8%
  • Clinical Trial
    Dyspnea US
  • Kind: experimental
    • Percent: 11.8%
  • Kind: placebo
    • Percent: 9.6%
  • Clinical Trial
    Urinary Tract Infection US
  • Kind: experimental
    • Percent: 11.5%
  • Kind: placebo
    • Percent: 7.1%
  • Clinical Trial
    High alanine transaminase US
  • Kind: experimental
    • Percent: 11.1%
  • Kind: placebo
    • Percent: 10.4%
  • Clinical Trial
    Dyspepsia US
  • Kind: experimental
    • Percent: 11.1%
  • Kind: placebo
    • Percent: 5%
  • Clinical Trial
    Nasopharyngitis US
  • Kind: experimental
    • Percent: 10.7%
  • Kind: placebo
    • Percent: 8.1%
  • Clinical Trial
    Cough US
  • Kind: experimental
    • Percent: 10.6%
  • Kind: placebo
    • Percent: 7.6%
  • Clinical Trial
    Hematuria US
  • Kind: experimental
    • Percent: 10.3%
  • Kind: placebo
    • Percent: 5.6%
  • Clinical Trial
    Pyrexia US
  • Kind: experimental
    • Percent: 8.7%
  • Kind: placebo
    • Percent: 5.9%
  • Clinical Trial
    Hypertension US
  • Kind: experimental
    • Percent: 8.5%
  • Kind: placebo
    • Percent: 6.9%
  • Clinical Trial
    Rash US
  • Kind: experimental
    • Percent: 8.1%
  • Kind: placebo
    • Percent: 3.7%
  • Clinical Trial
    Arrhythmia US
  • Kind: experimental
    • Percent: 7.2%
  • Kind: placebo
    • Percent: 4.6%
  • Clinical Trial
    Urinary Frequency US
  • Kind: experimental
    • Percent: 7.2%
  • Kind: placebo
    • Percent: 5.1%
  • Clinical Trial
    High bilirubin US
  • Kind: experimental
    • Percent: 6.6%
  • Kind: placebo
    • Percent: 4.6%
  • Clinical Trial
    Groin Pain US
  • Kind: experimental
    • Percent: 6.6%
  • Kind: placebo
    • Percent: 4.1%
  • Clinical Trial
    Nocturia US
  • Kind: experimental
    • Percent: 6.2%
  • Kind: placebo
    • Percent: 4.1%
  • Clinical Trial
    Dyspepsia US
  • Kind: experimental
    • Percent: 6.1%
  • Kind: placebo
    • Percent: 3.3%
  • Clinical Trial
    Fracture US
  • Kind: experimental
    • Percent: 5.9%
  • Kind: placebo
    • Percent: 2.3%
  • Clinical Trial
    Falls US
  • Kind: experimental
    • Percent: 5.9%
  • Kind: placebo
    • Percent: 3.3%
  • Clinical Trial
    Upper Respiratory Tract Infection US
  • Kind: experimental
    • Percent: 5.4%
  • Kind: placebo
    • Percent: 2.5%
  • Clinical Trial
    Hypokalemia US
  • Kind: experimental
    • Percent: 4%
  • Clinical Trial
    Transaminase increased US
  • Kind: experimental
    • Percent: 4%
  • Clinical Trial
    Chest Pain US
  • Kind: experimental
    • Percent: 3.8%
  • Kind: placebo
    • Percent: 2.8%
  • Clinical Trial

    Contraindications

    • Regions: US
    • Patient Conditions:
        • Name: Pregnancy
        • Drugbank Id: DBCOND0018394

    Food Interactions

    Exercise caution with St. John's Wort. This herb induces CYP3A4 and may increase the serum levels of abiraterone.

    Take on an empty stomach. Take at least 1 hour before or 2 hours after eating as food may increase exposure to abiraterone by 4-fold.