Darolutamide is a next-generation
androgen receptor signaling inhibitor (ARSI) currently approved for the treatment of nonmetastatic
castration-resistant
prostate cancer (nmCRPC) and metastatic
hormone sensitive
prostate cancer (mHSPC). Studies suggest that
darolutamide also has the potential to be used to treat other stages of
prostate cancer (PC), suggesting that its indications will broaden in the near future. Since ARSIs show similar efficacy for the treatment of PC, pharmacokinetic properties of these drugs and patient characteristics could help physicians decide which
drug to select. This review provides an overview of the pharmacokinetic and pharmacodynamic properties of
darolutamide. One of the most important pharmacological advantages of
darolutamide is its low brain distribution and therefore limited seizure potential and central nervous system adverse effects. In addition,
darolutamide has little
drug-drug interaction potential and is unlikely to alter the exposure of other
cytochrome P450 or
P-glycoprotein substrates. Nevertheless, it may significantly increase the exposure of
breast cancer resistant
protein (BCRP) substrates. The limited solubility and bioavailability of
darolutamide increases when taken together with food, regardless of the fat content.
Darolutamide is excessively metabolized by oxidation and glucuronidation and excreted in the urine and feces. For this reason,
dose reduction is required in patients with moderate and severe renal or severe hepatic impairment. Although no exposure-response relationship was observed with
darolutamide, less advanced stages of PC showed better PSA response on treatment. Overall,
darolutamide has some advantageous pharmacological properties that may lead to its preferred use, when broader registered, in selected patients across different disease stages.