A prospective phase I multicentre randomized cross-over pharmacokinetic study to determine the effect of food on abiraterone pharmacokinetics

Abstract

PurposeAbiraterone acetate is used at a fixed oral dose of 1000 mg once daily (OD) taken fasted. By administering abiraterone acetate with food, a reduced dose can potentially be given while maintaining equivalent abiraterone exposure. Moreover, administering abiraterone acetate with a breakfast is considered more patient friendly. The aim of this study was to establish the bio-equivalent lower dose of abiraterone when taken with a continental breakfast (CB) compared to the standard intake of 1000 mg OD fasted.MethodsIn this phase I, randomized cross-over, multi-center study, abiraterone pharmacokinetics (PK) were evaluated in patients with metastatic castration-resistant prostate cancer who were treated for 14 days with 1000 mg abiraterone acetate taken fasted, followed by 14 days of treatment with 500 mg taken with a CB.Results14 patients were enrolled into the study, of whom 12 were eligible for PK analysis. The geometric mean ratio (GMR) (fed/fasted) was 0.88 (90% CI 0.73–1.07) for area-under-the-curve (AUC0–24h), 1.03 (90% CI 0.79–1.34) for Cmax and 0.81 (90% CI 0.60–1.10) for Ctrough, respectively. High inter-patient variability (> 50%) was found for all PK parameters under both intake conditions. Patients seemed to be slightly more satisfied about the intake of 500 mg abiraterone acetate when taken with a CB compared to 1000 mg fasted.ConclusionIn conclusion, a bioequivalent lower dose of abiraterone taken with food could not be established in our study. Although based on the absence of a exposure–toxicity relationship, the strict bioequivalence margins as defined by the FDA guidelines could be applied more flexible for abiraterone. Information on the effect of food on abiraterone pharmacokinetics as presented in our study can be used for patients with difficulties taken their medication fasted.Electronic supplementary materialThe online version of this article (10.1007/s00280-019-03952-w) contains supplementary material, which is available to authorized users.

Niraparib with androgen receptor-axis-targeted therapy in patients with metastatic castration-resistant prostate cancer: safety and pharmacokinetic results from a phase 1b study (BEDIVERE)

“…Niraparib exposure, when used in combination with AAP, was dose proportional, as reported previously for niraparib monotherapy; the time to maximum concentration was also similar (approximately 3–4 h) [ 29 ]. The abiraterone pharmacokinetics for the combination were also comparable to abiraterone 1000 mg monotherapy data [ 34 ].…”

AR-V7 as a Biomarker for Resistance to Treatment with Abiraterone/Enzalutamide in Three Latin American Countries: A Hypothetical Cost-Saving Analysis

“…This reduced dose was included as an alternative recommendation in the NCCN clinical practice guidelines for prostate cancer [17]. However, there is still debate over the bioavailability and benefits of low-dose versus standard regimens [34][35][36]. Assuming that efficacy is similar, widespread use of a low-dose abiraterone regimen would result in dramatic cost savings and greater population coverage of this treatment.…”

“…This reduced dose was included as an alternative recommendation in the NCCN clinical practice guidelines for prostate cancer [17]. However, there is still debate over the bioavailability and benefits of low-dose versus standard regimens [34][35][36]. Assuming that Step-by-step cost-saving analysis (in U.S.…”

Bioavailability Enhancement and Food Effect Elimination of Abiraterone Acetate by Encapsulation in Surfactant-Enriched Oil Marbles

“…The online version of this article (https://doi.org/10.1208/s12248-020-00505-5) contains supplementary material, which is available to authorized users. (3). This implies a need for the development of novel formulation strategies that would allow food effect elimination and thus safe dosing regimen for abiraterone acetate.…”

“…An example of such a hard-to-formulate drug is abiraterone acetate, a prodrug of androgen biosynthesis inhibitor abiraterone, marketed under the original brand name Zytiga ® and used as a medication for the treatment of metastatic castration-resistant prostate cancer (2). Abiraterone acetate has an extremely low bioavailability in the fasted state (estimated to be less than 10%) and exhibits a highly variable increase in bioavailability in the fed state (3)(4)(5). It has been reported that intake with high-fat meal leads to increase in overall exposures by approximately 17-and 10fold, in terms C max and AUC, respectively.…”