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Details

Stereochemistry ABSOLUTE
Molecular Formula C26H33NO2
Molecular Weight 391.5457
Optical Activity UNSPECIFIED
Defined Stereocenters 6 / 6
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ABIRATERONE ACETATE

SMILES

[H][C@@]12CC=C(C3=CC=CN=C3)[C@@]1(C)CC[C@@]4([H])[C@@]2([H])CC=C5C[C@H](CC[C@]45C)OC(C)=O

InChI

InChIKey=UVIQSJCZCSLXRZ-UBUQANBQSA-N
InChI=1S/C26H33NO2/c1-17(28)29-20-10-12-25(2)19(15-20)6-7-21-23-9-8-22(18-5-4-14-27-16-18)26(23,3)13-11-24(21)25/h4-6,8,14,16,20-21,23-24H,7,9-13,15H2,1-3H3/t20-,21-,23-,24-,25-,26+/m0/s1

HIDE SMILES / InChI

Description

Abiraterone acetate (trade name Zytiga) is a prodrug to the abiraterone, steroidal compound with antiandrogen activity and a 17 α-hydroxylase/C17,20-lyase (CYP17) inhibitor. It is indicated in combination with prednisone for the treatment of patients with metastatic castration-resistant prostate cancer. Abiraterone acetate is converted in vivo to abiraterone which inhibits CYP17, enzyme expressed in testicular, adrenal, and prostatic tumor tissues and required for androgen biosynthesis. Administration of this agent may suppress testosterone production by both the testes and the adrenals to castrate-range levels. Androgen sensitive prostatic carcinoma responds to treatment that decreases androgen levels. Androgen deprivation therapies, such as treatment with GnRH agonists or orchiectomy, decrease androgen production in the testes but do not affect androgen production by the adrenals or in the tumor.

CNS Activity

Originator

Approval Year

Targets

Primary TargetPharmacologyConditionPotency
110.0 nM [IC50]

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
ZYTIGA

Cmax

ValueDoseCo-administeredAnalytePopulation
226 ng/mL
1000 mg 1 times / day steady-state, oral
ABIRATERONE plasma
Homo sapiens
297 ng/mL
1000 mg single, oral
ABIRATERONE plasma
Homo sapiens
12.5 ng/mL
125 mg single, oral
ABIRATERONE plasma
Homo sapiens
50.2 ng/mL
1000 mg single, oral
ABIRATERONE plasma
Homo sapiens
60.6 ng/mL
1000 mg single, oral
ABIRATERONE plasma
Homo sapiens
85.7 ng/mL
1000 mg single, oral
ABIRATERONE plasma
Homo sapiens
71.9 ng/mL
1000 mg single, oral
ABIRATERONE plasma
Homo sapiens
64.5 ng/mL
2000 mg single, oral
ABIRATERONE plasma
Homo sapiens

AUC

ValueDoseCo-administeredAnalytePopulation
1173 ng × h/mL
1000 mg 1 times / day steady-state, oral
ABIRATERONE plasma
Homo sapiens
1562 ng × h/mL
1000 mg single, oral
ABIRATERONE plasma
Homo sapiens
177 ng × h/mL
125 mg single, oral
ABIRATERONE plasma
Homo sapiens
315 ng × h/mL
1000 mg single, oral
ABIRATERONE plasma
Homo sapiens
315 ng × h/mL
1000 mg single, oral
ABIRATERONE plasma
Homo sapiens
330 ng × h/mL
1000 mg single, oral
ABIRATERONE plasma
Homo sapiens
365 ng × h/mL
1000 mg single, oral
ABIRATERONE plasma
Homo sapiens
461 ng × h/mL
2000 mg single, oral
ABIRATERONE plasma
Homo sapiens

T1/2

ValueDoseCo-administeredAnalytePopulation
18.6 h
1000 mg single, oral
ABIRATERONE plasma
Homo sapiens
18.2 h
125 mg single, oral
ABIRATERONE plasma
Homo sapiens
18.2 h
1000 mg single, oral
ABIRATERONE plasma
Homo sapiens
18.2 h
1000 mg single, oral
ABIRATERONE plasma
Homo sapiens
13.1 h
1000 mg single, oral
ABIRATERONE plasma
Homo sapiens
17.7 h
1000 mg single, oral
ABIRATERONE plasma
Homo sapiens
15.4 h
2000 mg single, oral
ABIRATERONE plasma
Homo sapiens

Doses

AEs

Overview

Drug as perpetrator​

Drug as victim

PubMed

Sample Use Guides

In Vivo Use Guide
1,000 mg (four 250 mg tablets) administered orally once daily in combination with prednisone 5 mg administered orally twice daily. Zytiga must be taken on an empty stomach. No food should be consumed for at least two hours before the dose of Zytiga is taken and for at least one hour after the dose of Zytiga is taken. For patients with baseline moderate hepatic impairment (Child-Pugh Class B), reduce the Zytiga starting dose to 250 mg once daily. For patients who develop hepatotoxicity during treatment, hold Zytiga until recovery. Retreatment may be initiated at a reduced dose. Zytiga should be discontinued if patients develop severe hepatotoxicity.
Route of Administration: Oral
In Vitro Use Guide
Abiraterone acetate (CB 7630) inhibits CYP17 with an IC50 of 110 nM in human testicular microsomes. In Caco-2 cell monolayers abiraterone acetate had a low apparent permeability and was not substrate of P-glycoprotein (P-gp). Abiraterone acetate inhibited P-gp significantly at high concentrations with a 50 % inhibitory concentration (IC50) of 10.8 uM however as abiraterone acetate is rapidly converted to abiraterone, no systemic inhibition of P-gp is expected.