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
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
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
Cmax
AUC
T1/2
Doses
AEs
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
OverviewOther
Other Inhibitor | Other Substrate | Other Inducer |
---|---|---|
Drug as perpetrator
Drug as victim
PubMed
Sample Use Guides
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
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.