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
| Autor: | Alberto Bernareggi, Nataliya P. Chilingirova, Giada Rizzi, Tatiana Caccia, Valentino J. Stella, Galina Kurteva |
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| Rok vydání: | 2019 |
| Předmět: |
Adult
Male Quinuclidines Pyridines Vomiting medicine.drug_class medicine.medical_treatment Cmax Pharmaceutical Science Phases of clinical research 02 engineering and technology 030226 pharmacology & pharmacy 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Pharmacokinetics Neoplasms medicine Humans Netupitant Antiemetic Aged Chemotherapy business.industry Palonosetron Nausea Middle Aged Isoquinolines 021001 nanoscience & nanotechnology Drug Combinations chemistry Anesthesia Antiemetics Administration Intravenous Female 0210 nano-technology business medicine.drug Chemotherapy-induced nausea and vomiting |
| Zdroj: | European Journal of Pharmaceutical Sciences. 139:105041 |
| ISSN: | 0928-0987 |
| DOI: | 10.1016/j.ejps.2019.105041 |
| Popis: | 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 (Cmax) was reached at the end of infusion and decreased to 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. |
| Databáze: | OpenAIRE |
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