Effect of Food on Abiraterone Pharmacokinetics: A Review

Figures & data

Table 1. Overview of clinical studies evaluating food effect on abiraterone pharmacokinetics.

Study	AA dose	Formulation	Study design	Population	Food condition	Ref.
COU-AA-001	Single dose (1000 or 2000 mg)^†	Capsule (preliminary formulation)	Phase I open-label, randomized, two-period crossover (tested 5 days apart)	Chemo-naive CRPC patients N = 9	Overnight fasted or high-fat meal	[11]
COU-AA-002	Single dose (250, 500, 750 or 1000 mg)	Tablet (preliminary formulation)	Phase I dose-escalation	Chemo-naive CRPC patients N = 33	Overnight fasted vs fed state^‡	[10]
COU-AA-009	Single dose (1000 mg)	Tablet (commercial formulation)	Phase I, open-label, randomized, three-period, crossover (7-day washout between periods)	Healthy subjects N = 36	Overnight fasted, low-fat meal or high-fat meal	[16]
212082PCR1005	Single dose (1000 mg)	Tablet (commercial formulation)	Phase I, open-label, randomized four-period crossover evaluating food timing (14-day washout between periods)	Healthy subjects N = 51	Overnight fasted; Medium-fat meal given at varying times before and/or after dosing^§	[18]
212082PCR2008	Multiple doses (1000 mg/day)	Tablet (commercial formulation)	Phase II, randomized, open-label, two-period, multicenter study evaluating food safety	mCRPC patients N = 25	Modified fasted (days 1–7); Low-fat meal vs high-fat meal (days 8–14)	[16]
C0U-AA-301	Multiple doses (1000 mg/day)^¶	Tablet (commercial formulation)	Phase III, double-blind, randomized, multicenter study evaluating efficacy and safety	mCRPC patients postchemo N = 1195	Modified fasted^#	[3]
COU-AA-302	Multiple doses (1000 mg/day)^¶	Tablet (commercial formulation)	Phase III, double-blind, randomized, multicenter study evaluating efficacy and safety	mCRPC patients pre-chemo N = 1088	Modified fasted^#	[13]

^†Abiraterone acetate was co-administered with the mineralocorticoid receptor antagonist eplerenone 50 to 200 mg/day.

^‡Abiraterone acetate was taken 30 min after an 800 to 1000 calorie, high-fat meal (50% of total caloric content).

^§Abiraterone acetate was given under four conditions after an overnight fast followed by a standardized medium-fat meal at 4 h post-dose, 1 and 4 h post-dose, 2 h pre-dose and 4 h post-dose, or 2 h pre-dose and 2 h post-dose.

^¶Abiraterone acetate was co-administered with 5 mg twice-daily prednisone for studies COU-AA-301 and COU-AA-302.

^#Abiraterone acetate was taken at least 1 h before a meal or 2 h after a meal.

AA: Abiraterone acetate; Chemo: Chemotherapy; CRPC: Castration-resistant prostate cancer; mCRPC: Metastatic CRPC.

Figure 1. Fat content of food impacts abiraterone exposure.

Mean (standard deviation) abiraterone plasma concentration–time curves (log-linear scale) following a single 1000-mg dose of abiraterone acetate in a fasted state, with a low-fat meal, or with a high-fat meal in healthy subjects.

Figure 2. Food timing impacts abiraterone exposure.

Effect of food timing on the mean (standard deviation) plasma concentration–time profiles of abiraterone.

Adapted with permission from [18] © Springer (2015).

Figure 3. Increase in abiraterone exposure observed after repeated abiraterone acetate dosing with a high-fat meal or low-fat meal compared with modified fasted state.

(A) Arithmetic mean (standard deviation) abiraterone plasma concentration–time profile (log-linear scale) under Day 7 modified fasted conditions or Day 14 low-fat meal. (B) Arithmetic mean (standard deviation) abiraterone plasma concentration–time profile (log-linear scale) under Day 7 modified fasted conditions or Day 14 high-fat meal.

Figure 4. The effect of food and food timing on abiraterone pharmacokinetics in studies with metastatic castration-resistant prostate cancer patients and healthy subjects.

The values are reported as the arithmetic mean ± standard error of the mean. A standard meal was given 4 h post-AA dose in all studies.

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