Increasing the efficacy of abiraterone - from pharmacokinetics, through therapeutic drug monitoring to overcoming food effects with innovative pharmaceutical products.

ABSTRACT

Current guidelines suggest radiotherapy as a first-line treatment for prostate cancer, along with prostatectomy, and androgen deprivation therapy. Abiraterone is a first-in-class medicinal product recommended in the treatment of metastatic castration resistant prostate cancer (mCRPC) that targets androgen receptors and inhibits systemic synthesis. However, successful therapy with this drug may pose some challenges. It has to be administered as an inactive prodrug - abiraterone acetate. It is also dissolved and absorbed poorly with large interindividual variability and exhibits considerable food effects. Additionally, the recommended daily dose of the drug is high (1000 mg abiraterone acetate), and the cost of the therapy is burdensome. The following review focuses on the strategies to optimize therapy with abiraterone acetate. First, it summarizes current findings on abiraterone pharmacokinetics and accentuates the need for utilizing therapeutic monitoring in clinical practice. Next, it extensively describes the options for improving the low bioavailability of the drug. The two major approaches are the utilization of the positive food effect to increase the exposure and development of supergenerics. The review emphasizes how different formulation approaches lead to increased solubility and impact the outcomes of pre-clinical and clinical trials. The review concludes with a discussion on possible future directions that may lead to the increase of the therapeutic efficacy of abiraterone.