Rolapitant

Absorption

Following administration of rolapitant, plasma concentrations reached peak levels in about 4 hours.

Toxicity

Most common adverse reactions occurring in >3% of patients receiving moderately emetogenic chemotherapy and combinations of anthracycline and cyclophosphamide included decreased appetite, neutropenia, dizziness, dyspepsia, urinary tract infection, stomatitis, and anemia. Most common adverse reactions occurring in patients receiving cisplatin-based highly emetogenic chemotherapy included neutropenia, hiccups, and abdominal pain.

Background

Rolapitant is a potent, highly selective, long-acting Neurokinin-1 (NK-1) receptor antagonist approved for the prevention of delayed chemotherapy-induced nausea and vomiting (CINV) in adults. Delayed-phase CINV typically occurs >24 hours after chemotherapy treatment and is principally mediated by Neurokinin-1 and its ligand Substance P, which is released in the gut following chemotherapy administration. Neurokinin-1 is also known as Tachykinin Receptor 1 (TACR1), Neurokinin 1 Receptor (NK1R), and Substance P Receptor (SPR). By blocking Substance P from interacting with NK-1 receptors in the gut and the central nervous system, rolapitant prevents late-phase CINV. Unlike other available NK-1 receptor antagonists, rolapitant is not an inhibitor of Cytochrome P450 enzyme CYP3A4 and has a long elimination half-life, allowing a single dose to prevent both acute and late-phase CINV during the first 120 hours post-chemotherapy.

Indications

This drug is indicated in adults in combination with other antiemetics for the prevention of delayed nausea and vomiting associated with emetogenic chemotherapy.

Definition

ChEBI: An azaspiro compound that is 1,7-diazaspiro[4.5]decan-2-one carrying additional phenyl and 1-{[3,5-bis(trifluoromethyl)phenyl]ethoxy}methyl substituents at position 8. Used (in the form of the hydrochloride hydrate) for the prevention of delayed nausea and vomiting associated with initial and repeat courses of emetogenic cancer chemotherapy.

Metabolism

Rolapitant is metabolized primarily by Cytochrome P450 enzyme 3A4 (CYP3A4) to its major active and circulating metabolite M19 (C4-pyrrolidine-hydroxylated rolapitant).