Drug-Drug Interaction (Ddi) Of Darolutamide With Cytochrome P450 (Cyp) And P-Glycoprotein (P-Gp) Substrates: Results From Clinical And In Vitro Studies.
JOURNAL OF CLINICAL ONCOLOGY(2019)
Abstract
297Background: Maintaining quality of survival, by delaying disease progression and minimizing therapy burden, is critical for patients and has been evaluated in the pivotal phase III ARAMIS study in patients with non-metastatic castration-resistant prostate cancer. Due to comorbidity, elderly men often receive multiple comedications, including CYP and P-gp substrates, eg, simvastatin and digoxin. Enzalutamide and apalutamide, approved androgen receptor (AR) inhibitors, are strong CYP3A4 inducers and thus have potential for CYP-mediated DDIs. The effect of darolutamide, a structurally unique AR antagonist, on CYP activity (in vitro and in vivo) and P-gp activity (in vivo) was assessed. Methods: Inhibition of CYP isoforms by Daro was investigated in human liver microsomes using standard substrates. In addition, CYP and P-gp activity during darolutamide treatment was studied in a phase I trial of 15 healthy men who received 75 mg dabigatran etexilate (DABE, P-gp substrate) + 1 mg midazolam (MDZ, CYP3A4 subs...
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Key words
darolutamide,cytochrome p450,drug-drug,p-glycoprotein
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