Enzalutamide Reduces Oxycodone Exposure in Men with Prostate Cancer

Springer Science and Business Media LLC - Tập 62 - Trang 989-996 - 2023

S. E. H. Detert Oude Weme¹, L. M. G. Hulskotte^1,2, W. L. Vervenne³, A. L. T. Imholz³, R. G. H. M. Cremers⁴, K. Taxis², A. K. L. Reyners⁵, I. R. F. van Berlo-van de Laar¹, F. G. A. Jansman^1,2, G. E. Benoist¹

¹Department of Clinical Pharmacy, Deventer Teaching Hospital, Deventer, The Netherlands

²Unit of PharmacoTherapy, -Epidemiology &-Economics, Groningen Research Institute of Pharmacy (GRIP), University of Groningen, Groningen, the Netherlands

³Department of Medical Oncology, Deventer Teaching Hospital, Deventer, The Netherlands

⁴Department of Urology, Deventer Teaching Hospital, Deventer, The Netherlands

⁵Department of Medical Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands

Tóm tắt

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 AUC0–8 h and Cmax of oxycodone with, respectively, 44.7% (p < 0.001) and 35.5% (p = 0.004) compared with the control arm. The AUC0–8 h and Cmax 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, AUC0–8 h and Cmax of the inactive metabolites noroxycodone and noroxymorphone were significantly increased by enzalutamide. 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.

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