Abiraterone is a selective inhibitor of androgen biosynthesis that potently and irreversibly
blocks CYP17, a crucial enzyme in testosterone and estrogen synthesis. A pro-drug of
abiraterone, abiraterone acetate (Zytiga®), was developed to overcome its poor
bio-availability and is fully converted to the active moiety abiraterone. Abiraterone acetate
tablets are administered at a fixed oral dose of 1000mg QD in a fasted state in combination
with 10mg prednisolon daily.
Abiraterone acetate has a low solubility in aqueous media and a low permeability. The
bioavailability of abiraterone acetate is significantly influenced when ingested with food.
Ingesting abiraterone acetate with a low fat or a high fat meal resulted respectively in a 5-
or 10-fold increase in AUC0-∞. The high and low fat FDA meals used in these food effect
studies differ largely from breakfasts taken in everyday life (ca. 800-1000 cal). A
continental breakfast contains 160 to 320 calories of which 25-50% is fat, is more compatible
with a normal lifestyle and therefore easily sustainable in daily practice. However, the
effect of a continental breakfast on the absorption of abiraterone is unknown yet.
Furthermore, increasing healthcare costs are a growing concern in all developed countries.
Therefore effort should be invested to keep anticancer treatment affordable. A food
intervention resulting in a better absorption and enhanced exposure to abiraterone, can lead
to a reduced dose, which could significantly impact health care costs for a tumor which is as
prevalent as metastatic prostate cancer.
Therefore the investigators want to perform a bioequivalent study to investigate what dose of
abiraterone with a continental breakfast equals the dose of 1000mg taken in fasted