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 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.
Department of Clinical Pharmacy, Radboud University Medical Centre, Route 864, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands.
Guillemette E
GE
Benoist
Department of Urology, Radboud University Medical Centre, Nijmegen, The Netherlands.
Rianne J
RJ
Hendriks
Department of Urology, Radboud University Medical Centre, Nijmegen, The Netherlands.
Peter F A
PF
Mulders
Department of Medical Oncology, Radboud University Medical Centre, Nijmegen, The Netherlands.
Winald R
WR
Gerritsen
Department of Urology, Canisius Wilhelmina Hospital, Nijmegen, The Netherlands.
Diederik M
DM
Somford
Department of Urology, Radboud University Medical Centre, Nijmegen, The Netherlands.
Jack A
JA
Schalken
Department of Urology, Radboud University Medical Centre, Nijmegen, The Netherlands.
Inge M
IM
van Oort
Department of Clinical Pharmacy, Radboud University Medical Centre, Route 864, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands.
David M
DM
Burger
Department of Clinical Pharmacy, Radboud University Medical Centre, Route 864, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands. nielka.vanerp@radboudumc.nl.
Nielka P
NP
van Erp
D000069501:Abiraterone Acetate / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019540:Area Under Curve; D001549:Benzamides; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004790:Enzyme Induction / Q000187:drug effects; D005215:Fasting; D006207:Half-Life; D006801:Humans; D017093:Liver Failure / Q000378:metabolism; D008297:Male; D008657:Metabolic Clearance Rate; D009570:Nitriles; D010669:Phenylthiohydantoin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy*; D011944:Receptors, Androgen / Q000187:drug effects
D000970:Antineoplastic Agents; D001549:Benzamides; D009570:Nitriles; D011944:Receptors, Androgen; D010669:Phenylthiohydantoin; D003577:Cytochrome P-450 Enzyme System; C540278:enzalutamide; D000069501:Abiraterone Acetate