Back to Search
Start Over
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.
- Source :
-
European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences [Eur J Pharm Sci] 2019 Nov 01; Vol. 139, pp. 105041. Date of Electronic Publication: 2019 Aug 09. - Publication Year :
- 2019
-
Abstract
- NEPA is the fixed combination antiemetic composed of the neurokinin-1 receptor antagonist netupitant and the 5-hydroxytryptamine-3 receptor antagonist palonosetron. The intravenous (i.v.) formulation of NEPA (fosnetupitant 235 mg/palonosetron 0.25 mg) was developed to enhance the convenience of NEPA administration. In a phase 3 study, i.v. NEPA showed acceptable safety with low risk for injection-site reactions. 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 (C <subscript>max</subscript> ) was reached at the end of infusion and decreased to <1% of C <subscript>max</subscript> 30 min later. Netupitant was rapidly released from its prodrug and C <subscript>max</subscript> of 590 ng/ml was reached at the end of fosnetupitant infusion, with a mean exposure (AUC <subscript>∞</subscript> ) of 15,588 h∙ng/ml. Palonosetron C <subscript>max</subscript> was reached at the end of infusion, with a mean AUC <subscript>∞</subscript> 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.<br /> (Copyright © 2019. Published by Elsevier B.V.)
- Subjects :
- Administration, Intravenous
Adult
Aged
Antiemetics administration & dosage
Antiemetics adverse effects
Antiemetics blood
Drug Combinations
Female
Humans
Isoquinolines administration & dosage
Isoquinolines adverse effects
Isoquinolines blood
Male
Middle Aged
Nausea chemically induced
Nausea prevention & control
Neoplasms drug therapy
Pyridines administration & dosage
Pyridines adverse effects
Pyridines blood
Quinuclidines administration & dosage
Quinuclidines adverse effects
Quinuclidines blood
Vomiting chemically induced
Vomiting prevention & control
Antiemetics pharmacokinetics
Isoquinolines pharmacokinetics
Neoplasms metabolism
Pyridines pharmacokinetics
Quinuclidines pharmacokinetics
Subjects
Details
- Language :
- English
- ISSN :
- 1879-0720
- Volume :
- 139
- Database :
- MEDLINE
- Journal :
- European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences
- Publication Type :
- Academic Journal
- Accession number :
- 31404621
- Full Text :
- https://doi.org/10.1016/j.ejps.2019.105041