Pharmacokinetic profile and safety of intravenous NEPA, a fixed combination of fosnetupitant and palonosetron, in cancer patients: Prevention of chemotherapy-induced nausea and vomiting associated with highly emetogenic chemotherapy.

This study evaluated the pharmacokinetics and safety of i.v. NEPA in cancer patients. This was a single-center, single-dose phase 1 study in patients receiving highly emetogenic chemotherapy. Patients received a 30-min infusion of i.v. NEPA plus oral dexamethasone (12 mg) prior to chemotherapy, and oral dexamethasone (8 mg/daily) on days 2-4. Twenty-four patients received the complete i.v. NEPA infusion volume. Fosnetupitant maximum plasma concentration (Cmax) was reached at the end of infusion and decreased to <1% of Cmax 30 min later. Netupitant was rapidly released from its prodrug and Cmax of 590 ng/ml was reached at the end of fosnetupitant infusion, with a mean exposure (AUC∞) of 15,588 h∙ng/ml. Palonosetron Cmax was reached at the end of infusion, with a mean AUC∞ of 36.07 h∙ng/ml. The most common adverse events were constipation (29%), nausea (17%), and vasospasm (8%). No i.v. NEPA-related injection site reactions occurred. Fosnetupitant conversion to netupitant occurred rapidly in cancer patients. Netupitant and palonosetron pharmacokinetic profiles in i.v. NEPA were similar to those reported for oral NEPA. i.v. NEPA was well tolerated with a similar safety profile to oral NEPA. i.v. NEPA provides additional administration convenience. Clinical trial registration number: EudraCT 2015-004750-18. PMID: 31404621 [PubMed - as supplied by publisher]
Source: European Journal of Pharmaceutical Sciences - Category: Drugs & Pharmacology Authors: Tags: Eur J Pharm Sci Source Type: research