Enzalutamide Reduces Oxycodone Exposure in Men with Prostate Cancer.
Journal
Clinical pharmacokinetics
ISSN: 1179-1926
Titre abrégé: Clin Pharmacokinet
Pays: Switzerland
ID NLM: 7606849
Informations de publication
Date de publication:
07 2023
07 2023
Historique:
accepted:
18
04
2023
medline:
14
7
2023
pubmed:
10
5
2023
entrez:
10
5
2023
Statut:
ppublish
Résumé
Up to 90% of patients with castration-resistant prostate cancer (CRPC) will develop symptomatic bone metastases requiring pain medication, with opioids being the mainstay of therapy in treating moderate and severe pain. Enzalutamide is an androgen receptor antagonist for the treatment of CRPC and a strong inducer of cytochrome P450 (CYP)3A4. Hereby, enzalutamide potentially reduces the exposure of oxycodone, an opioid metabolized by CYP3A4 and CYP2D6. Our objective was to evaluate the potential drug-drug interaction of enzalutamide and oxycodone. A prospective, nonrandomized, open-label, two-arm parallel study was performed. All patients received a single dose of 15 mg normal-release oxycodone. Patients in the enzalutamide arm (ENZ-arm) received enzalutamide 160 mg once daily. Plasma concentrations of oxycodone and its metabolites were quantified using a validated liquid chromatography with tandem mass spectrometry (LC-MS/MS) method. Twenty-six patients (13 ENZ-arm; 13 control arm) were enrolled in the study. Enzalutamide decreased the mean AUC Co-administration of enzalutamide significantly reduced exposure to oxycodone and its active metabolite oxymorphone in men with prostate cancer. This should be taken into account when prescribing enzalutamide combined with oxycodone.
Sections du résumé
BACKGROUND AND OBJECTIVE
Up to 90% of patients with castration-resistant prostate cancer (CRPC) will develop symptomatic bone metastases requiring pain medication, with opioids being the mainstay of therapy in treating moderate and severe pain. Enzalutamide is an androgen receptor antagonist for the treatment of CRPC and a strong inducer of cytochrome P450 (CYP)3A4. Hereby, enzalutamide potentially reduces the exposure of oxycodone, an opioid metabolized by CYP3A4 and CYP2D6. Our objective was to evaluate the potential drug-drug interaction of enzalutamide and oxycodone.
METHODS
A prospective, nonrandomized, open-label, two-arm parallel study was performed. All patients received a single dose of 15 mg normal-release oxycodone. Patients in the enzalutamide arm (ENZ-arm) received enzalutamide 160 mg once daily. Plasma concentrations of oxycodone and its metabolites were quantified using a validated liquid chromatography with tandem mass spectrometry (LC-MS/MS) method.
RESULTS
Twenty-six patients (13 ENZ-arm; 13 control arm) were enrolled in the study. Enzalutamide decreased the mean AUC
CONCLUSION
Co-administration of enzalutamide significantly reduced exposure to oxycodone and its active metabolite oxymorphone in men with prostate cancer. This should be taken into account when prescribing enzalutamide combined with oxycodone.
Identifiants
pubmed: 37162620
doi: 10.1007/s40262-023-01255-1
pii: 10.1007/s40262-023-01255-1
pmc: PMC10338391
doi:
Substances chimiques
Oxycodone
CD35PMG570
Oxymorphone
9VXA968E0C
enzalutamide
93T0T9GKNU
Analgesics, Opioid
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
989-996Informations de copyright
© 2023. The Author(s).
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