Pharmacokinetic Aspects of the Two Novel Oral Drugs Used for Metastatic Castration-Resistant Prostate Cancer: Abiraterone Acetate and Enzalutamide.
Article Details
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Benoist GE, Hendriks RJ, Mulders PF, Gerritsen WR, Somford DM, Schalken JA, van Oort IM, Burger DM, van Erp NP
Pharmacokinetic Aspects of the Two Novel Oral Drugs Used for Metastatic Castration-Resistant Prostate Cancer: Abiraterone Acetate and Enzalutamide.
Clin Pharmacokinet. 2016 Nov;55(11):1369-1380. doi: 10.1007/s40262-016-0403-6.
- PubMed ID
- 27106175 [ View in PubMed]
- Abstract
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.
DrugBank Data that Cites this Article
- Drug Enzymes
Drug Enzyme Kind Organism Pharmacological Action Actions Abiraterone Cytochrome P450 1A2 Protein Humans UnknownInhibitorDetails - Drug Transporters
Drug Transporter Kind Organism Pharmacological Action Actions Abiraterone Multidrug resistance-associated protein 1 Protein Humans UnknownInhibitorDetails - Drug Reactions
Reaction Details
