Abiraterone Acetate (abiraterone acetate)

Abiraterone acetate is a prodrug of abiraterone, a potent, selective, and irreversible inhibitor of cytochrome P-450 (CYP) 17alpha-hydroxylase/C17,20-lyase (also referred to as CYP17); abiraterone is an antineoplastic agent.

Abiraterone acetate is a prodrug of abiraterone, a potent, selective, and irreversible inhibitor of cytochrome P-450 (CYP) 17alpha-hydroxylase/C17,20-lyase (also referred to as CYP17); abiraterone is an antineoplastic agent. The CYP17 enzyme is expressed in the testes and adrenal glands, and also is expressed in prostatic tumor tissue. CYP17 catalyzes 2 sequential reactions: 17alpha-hydroxylase catalyzes the conversion of pregnenolone and progesterone to their 17alpha-hydroxy derivatives, and C17,20-lyase catalyzes the conversion of these 17alpha-hydroxy derivatives to dehydroepiandrosterone (DHEA) and androstenedione.

DHEA and androstenedione are androgenic precursors of testosterone. Testosterone and dihydrotestosterone bind to and activate the androgen receptor, which is key in the development and progression of prostate cancer. Thus, inhibition of CYP17 activity by abiraterone results in suppression of androgen production.

Inhibition of CYP17 activity by abiraterone also can result in increased mineralocorticoid synthesis by the adrenal glands and subsequent risk of hypertension, hypokalemia, and fluid retention. Abiraterone is tenfold to 30-fold more potent than ketoconazole (a nonspecific CYP inhibitor and weak inhibitor of CYP17) in its inhibition of the CYP17 enzyme.

Although decreases in serum testosterone and other androgens have been observed with abiraterone acetate therapy for prostate cancer, it is not necessary to monitor the effect of abiraterone on serum testosterone levels. Changes in serum prostate specific antigen (PSA) concentrations also may be observed, but have not been shown to correlate with clinical benefit in individual patients.

Following oral administration, abiraterone acetate is hydrolyzed, most likely by esterases in non-CYP-dependent pathways, to its active metabolite, abiraterone. Peak plasma concentrations of abiraterone occur 2 hours after administration of the parent drug. Abiraterone is further metabolized to form 2 inactive sulfate conjugates, abiraterone sulfate (formed by SULT2A1, a sulfotransferase that catalyzes the sulfate conjugation of DHEA and other steroids) and N-oxide abiraterone sulfate (formed by CYP3A4 and SULT2A1).

The mean terminal half-life of abiraterone in patients with metastatic castration-resistant prostate cancer is 12 hours. Following oral administration of a radiolabeled dose of abiraterone acetate, about 88% of the dose is recovered in feces, mainly as abiraterone acetate (55%) and abiraterone (22%), and 5% of the dose is recovered in urine.

Systemic exposure to abiraterone is dose proportional over a dose range of 250 mg to 1 g (conventional abiraterone) and 125 mg to 625 mg (micronized abiraterone); however, systemic exposure to abiraterone did not substantially increase when the dose of the conventional formulation was doubled from 1 g to 2 g.

Systemic exposure to abiraterone is increased when abiraterone acetate is administered with food. Oral administration of a single 1-g dose of abiraterone acetate (conventional) with a low-fat or high-fat meal resulted in increases in systemic exposure of approximately fivefold or tenfold, respectively, and increases in peak plasma concentrations of approximately sevenfold or 17-fold, respectively, compared with administration in the fasted state. When a single dose of abiraterone acetate (conventional) was administered 2 hours after or 1 hour before a medium-fat meal, systemic exposure of abiraterone increased approximately sevenfold or 1.6-fold, respectively, compared with administration in the fasted state.

In patients with metastatic castration-resistant prostate cancer, systemic exposure to abiraterone was similar following administration of abiraterone acetate (conventional) for 7 days with a low-fat meal or at least 2 hours after or 1 hour before a meal, but increased approximately twofold when administered with a high-fat meal. Oral administration of a single 500-mg dose of abiraterone acetate (micronized) with a high-fat meal resulted in increases in systemic exposure and peak plasma concentrations of approximately 4.4-fold and 6.5-fold, respectively, compared with administration in the fasted state. The bioavailability of the micronized formulation of abiraterone acetate is less variable compared with the conventional formulation; therefore, the micronized formulation may be administered without regard to food.

Conventional abiraterone acetate must be administered on an empty stomach; no food should be consumed for at least 2 hours before or 1 hour after a dose.

Abiraterone is a potent inhibitor of CYP isoenzymes 1A2 and 2D6 and a moderate inhibitor of CYP isoenzymes 2C9, 2C19, and 3A4/5. In vitro studies indicate that neither abiraterone acetate nor abiraterone is a substrate of P-glycoprotein (P-gp); however, abiraterone acetate is an inhibitor of P-gp.

USES: This medication is used to treat prostate cancer. Abiraterone belongs to a class of drugs known as anti-androgens (anti-testosterone). Testosterone, a natural hormone, helps prostate cancer to grow and spread.

Abiraterone works by blocking the production of testosterone, thereby slowing the growth and spread of prostate cancer. This medication should not be given to women or children.

Generic name: abiraterone acetate
Pronunciation: (A-bir-A-ter-one)

The following indications are listed for Abiraterone Acetate:

• Metastatic Castration-Resistant Prostate Cancer
• Metastatic Castration-Sensitive Prostate Cancer

Also known as: Metastatic Hormone Refractory Prostate Cancer, Metastatic Hormone Sensitive Prostate Cancer.

No ICD codes are available for this drug.