title: Food effects on abiraterone pharmacokinetics in healthy subjects and patients with metastatic castration-resistant prostate cancer.
abstract: Food effect on abiraterone pharmacokinetics and safety on abiraterone acetate coadministration with low-fat or high-fat meals was examined in healthy subjects and metastatic castration-resistant prostate cancer (mCRPC) patients. Healthy subjects (n = 36) were randomized to abiraterone acetate (single dose, 1000 mg) + low-fat meal, + high-fat meal, and fasted state. mCRPC patients received repeated doses (abiraterone acetate 1000 mg + 5 mg prednisone twice daily; days 1-7) in a modified fasting state followed by abiraterone acetate plus prednisone within 0.5 hours post-low-fat (n = 6) or high-fat meal (n = 18; days 8-14). In healthy subjects, geometric mean (GM) abiraterone area under plasma concentration-time curve (AUC) increased ∼5- and ∼10-fold, respectively, with low-fat and high-fat meals versus fasted state (GM [coefficient of variation], 1942 [48] and 4077 [37] ng · h/mL vs 421 [67] ng · h/mL, respectively). In mCRPC patients, abiraterone AUC was ∼2-fold higher with a high-fat meal and similar with a low-fat meal versus modified fasting state (GM [coefficient of variation]: 1992 [34] vs 973 [58] ng · h/mL and 1264 [65] vs 1185 [90] ng · h/mL, respectively). Adverse events (all grade ≤ 3) were similar, with high-fat/low-fat meals or fasted/modified fasting state. Short-term dosing with food did not alter abiraterone acetate safety.
authors.affiliation: BC Cancer Agency, Vancouver, BC, Canada.
authors.forename: Kim N
authors.initials: KN
authors.lastname: Chi
authors.affiliation: Cross Cancer Institute, Edmonton, AB, Canada.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Spratlin
authors.affiliation: BC Cancer Agency, Vancouver, BC, Canada.
authors.forename: Christian
authors.initials: C
authors.lastname: Kollmannsberger
authors.affiliation: Cross Cancer Institute, Edmonton, AB, Canada.
authors.forename: Scott
authors.initials: S
authors.lastname: North
authors.affiliation: BC Cancer Agency, Vancouver, BC, Canada.
authors.forename: Catherine
authors.initials: C
authors.lastname: Pankras
authors.affiliation: Janssen Research & Development, Raritan, NJ, USA.
authors.forename: Martha
authors.initials: M
authors.lastname: Gonzalez
authors.affiliation: Janssen Research & Development, Raritan, NJ, USA.
authors.forename: Apexa
authors.initials: A
authors.lastname: Bernard
authors.affiliation: Janssen Research & Development, Beerse, Belgium.
authors.forename: Hans
authors.initials: H
authors.lastname: Stieltjes
authors.affiliation: Janssen Research & Development, Raritan, NJ, USA.
authors.forename: Lixian
authors.initials: L
authors.lastname: Peng
authors.affiliation: Janssen Research & Development, Raritan, NJ, USA.
authors.forename: James
authors.initials: J
authors.lastname: Jiao
authors.affiliation: Janssen Research & Development, Raritan, NJ, USA.
authors.forename: Milin
authors.initials: M
authors.lastname: Acharya
authors.affiliation: Janssen Research & Development, San Diego, CA, USA.
authors.forename: Thian
authors.initials: T
authors.lastname: Kheoh
authors.affiliation: Janssen Research & Development, Los Angeles, CA, USA.
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Griffin
authors.affiliation: Janssen Research & Development, Los Angeles, CA, USA.
authors.forename: Margaret K
authors.initials: MK
authors.lastname: Yu
authors.affiliation: Janssen Research & Development, Titusville, NJ, USA.
authors.forename: Caly
authors.initials: C
authors.lastname: Chien
authors.affiliation: Janssen Research & Development, Los Angeles, CA, USA.
authors.forename: Nam Phuong
authors.initials: NP
authors.lastname: Tran
mesh_terms: D000069501:Abiraterone Acetate / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D065607:Cytochrome P-450 Enzyme Inhibitors / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics; D004041:Dietary Fats / Q000494:pharmacology*; D004359:Drug Therapy, Combination; D005215:Fasting / Q000378:metabolism; D005260:Female; D018565:Food-Drug Interactions; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D008875:Middle Aged; D011241:Prednisone / Q000009:adverse effects; D064129:Prostatic Neoplasms, Castration-Resistant / Q000097:blood / Q000378:metabolism*
chemical_list: D065607:Cytochrome P-450 Enzyme Inhibitors; D004041:Dietary Fats; D000069501:Abiraterone Acetate; D011241:Prednisone
keywords: abiraterone acetate; food effect; pharmacokinetic; safety