Détail du document
Identifiant
doi:10.1007/s40262-023-01255-1...
Auteur
Detert Oude Weme, S. E. H. Hulskotte, L. M. G. Vervenne, W. L. Imholz, A. L. T. Cremers, R. G. H. M. Taxis, K. Reyners, A. K. L. van Berlo-van de Laar, I. R. F. Jansman, F. G. A. Benoist, G. E.Langue
enEditeur
Springer
Catégorie
Medicine & Public Health
Année
2023
Date de référencement
17/05/2023
Mots clés
auc_0–8 h cancer enz-arm control 001 _max prostate exposure arm oxycodone enzalutamideRésumé
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_0–8 h and C _max of oxycodone with, respectively, 44.7% ( p < 0.001) and 35.5% ( p = 0.004) compared with the control arm.
The AUC_0–8 h and C _max of the active metabolite oxymorphone were 74.2% ( p < 0.001) and 56.0% ( p = 0.001) lower in the ENZ-arm compared with the control arm.
In contrast, AUC_0–8 h and C _max of the inactive metabolites noroxycodone and noroxymorphone were significantly increased by enzalutamide.
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.
Detert Oude Weme, S. E. H.,Hulskotte, L. M. G.,Vervenne, W. L.,Imholz, A. L. T.,Cremers, R. G. H. M.,Taxis, K.,Reyners, A. K. L.,van Berlo-van de Laar, I. R. F.,Jansman, F. G. A.,Benoist, G. E., 2023, Enzalutamide Reduces Oxycodone Exposure in Men with Prostate Cancer, Springer
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