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Pharmacokinetic Aspects of the Two Novel Oral Drugs Used for Metastatic Castration-Resistant Prostate Cancer: Abiraterone Acetate and Enzalutamide

Two novel oral drugs that target androgen signaling have recently become available for the treatment of metastatic castration-resistant prostate cancer (mCRPC). Abiraterone acetate inhibits the synthesis of the natural ligands of the androgen receptor, whereas enzalutamide directly inhibits the andr...

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Autores principales: Benoist, Guillemette E., Hendriks, Rianne J., Mulders, Peter F. A., Gerritsen, Winald R., Somford, Diederik M., Schalken, Jack A., van Oort, Inge M., Burger, David M., van Erp, Nielka P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer International Publishing 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5069300/
https://www.ncbi.nlm.nih.gov/pubmed/27106175
http://dx.doi.org/10.1007/s40262-016-0403-6
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author Benoist, Guillemette E.
Hendriks, Rianne J.
Mulders, Peter F. A.
Gerritsen, Winald R.
Somford, Diederik M.
Schalken, Jack A.
van Oort, Inge M.
Burger, David M.
van Erp, Nielka P.
author_facet Benoist, Guillemette E.
Hendriks, Rianne J.
Mulders, Peter F. A.
Gerritsen, Winald R.
Somford, Diederik M.
Schalken, Jack A.
van Oort, Inge M.
Burger, David M.
van Erp, Nielka P.
author_sort Benoist, Guillemette E.
collection PubMed
description Two novel oral drugs that target androgen signaling have recently become available for the treatment of metastatic castration-resistant prostate cancer (mCRPC). Abiraterone acetate inhibits the synthesis of the natural ligands of the androgen receptor, whereas enzalutamide directly inhibits the androgen receptor by several mechanisms. Abiraterone acetate and enzalutamide appear to be equally effective for patients with mCRPC pre- and postchemotherapy. Rational decision making for either one of these drugs is therefore potentially driven by individual patient characteristics. In this review, an overview of the pharmacokinetic characteristics is given for both drugs and potential and proven drug–drug interactions are presented. Additionally, the effect of patient-related factors on drug disposition are summarized and the limited data on the exposure–response relationships are described. The most important pharmacological feature of enzalutamide that needs to be recognized is its capacity to induce several key enzymes in drug metabolism. The potency to cause drug–drug interactions needs to be addressed in patients who are treated with multiple drugs simultaneously. Abiraterone has a much smaller drug–drug interaction potential; however, it is poorly absorbed, which is affected by food intake, and a large interpatient variability in drug exposure is observed. Dose reductions of abiraterone or, alternatively, the selection of enzalutamide, should be considered in patients with hepatic dysfunction. Understanding the pharmacological characteristics and challenges of both drugs could facilitate decision making for either one of the drugs.
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spelling pubmed-50693002016-11-02 Pharmacokinetic Aspects of the Two Novel Oral Drugs Used for Metastatic Castration-Resistant Prostate Cancer: Abiraterone Acetate and Enzalutamide Benoist, Guillemette E. Hendriks, Rianne J. Mulders, Peter F. A. Gerritsen, Winald R. Somford, Diederik M. Schalken, Jack A. van Oort, Inge M. Burger, David M. van Erp, Nielka P. Clin Pharmacokinet Review Article Two novel oral drugs that target androgen signaling have recently become available for the treatment of metastatic castration-resistant prostate cancer (mCRPC). Abiraterone acetate inhibits the synthesis of the natural ligands of the androgen receptor, whereas enzalutamide directly inhibits the androgen receptor by several mechanisms. Abiraterone acetate and enzalutamide appear to be equally effective for patients with mCRPC pre- and postchemotherapy. Rational decision making for either one of these drugs is therefore potentially driven by individual patient characteristics. In this review, an overview of the pharmacokinetic characteristics is given for both drugs and potential and proven drug–drug interactions are presented. Additionally, the effect of patient-related factors on drug disposition are summarized and the limited data on the exposure–response relationships are described. The most important pharmacological feature of enzalutamide that needs to be recognized is its capacity to induce several key enzymes in drug metabolism. The potency to cause drug–drug interactions needs to be addressed in patients who are treated with multiple drugs simultaneously. Abiraterone has a much smaller drug–drug interaction potential; however, it is poorly absorbed, which is affected by food intake, and a large interpatient variability in drug exposure is observed. Dose reductions of abiraterone or, alternatively, the selection of enzalutamide, should be considered in patients with hepatic dysfunction. Understanding the pharmacological characteristics and challenges of both drugs could facilitate decision making for either one of the drugs. Springer International Publishing 2016-04-22 2016 /pmc/articles/PMC5069300/ /pubmed/27106175 http://dx.doi.org/10.1007/s40262-016-0403-6 Text en © The Author(s) 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/), which permits any noncommercial use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Review Article
Benoist, Guillemette E.
Hendriks, Rianne J.
Mulders, Peter F. A.
Gerritsen, Winald R.
Somford, Diederik M.
Schalken, Jack A.
van Oort, Inge M.
Burger, David M.
van Erp, Nielka P.
Pharmacokinetic Aspects of the Two Novel Oral Drugs Used for Metastatic Castration-Resistant Prostate Cancer: Abiraterone Acetate and Enzalutamide
title Pharmacokinetic Aspects of the Two Novel Oral Drugs Used for Metastatic Castration-Resistant Prostate Cancer: Abiraterone Acetate and Enzalutamide
title_full Pharmacokinetic Aspects of the Two Novel Oral Drugs Used for Metastatic Castration-Resistant Prostate Cancer: Abiraterone Acetate and Enzalutamide
title_fullStr Pharmacokinetic Aspects of the Two Novel Oral Drugs Used for Metastatic Castration-Resistant Prostate Cancer: Abiraterone Acetate and Enzalutamide
title_full_unstemmed Pharmacokinetic Aspects of the Two Novel Oral Drugs Used for Metastatic Castration-Resistant Prostate Cancer: Abiraterone Acetate and Enzalutamide
title_short Pharmacokinetic Aspects of the Two Novel Oral Drugs Used for Metastatic Castration-Resistant Prostate Cancer: Abiraterone Acetate and Enzalutamide
title_sort pharmacokinetic aspects of the two novel oral drugs used for metastatic castration-resistant prostate cancer: abiraterone acetate and enzalutamide
topic Review Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5069300/
https://www.ncbi.nlm.nih.gov/pubmed/27106175
http://dx.doi.org/10.1007/s40262-016-0403-6
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