Pharmacokinetics and safety evaluation of oral Palonosetron in Chinese healthy volunteers: A phase 1, open-label, randomized, cross-over study.

Purpose: Palonosetron hydrochloride is a specific 5-HT3 receptor antagonist, used to prevent chemotherapy-induced nausea and vomiting (CINV), and is a known chemical entity currently registered in the oral and IV forms in several countries worldwide.

Methods: Single-center, single-dose, 3-treatment, open-label, randomized, 3-period, phase-I cross-over study, conducted in 18 individuals (16 males and 2 females). The primary objective was to assess the pharmacokinetic profile of Palonosetron 0.

A phase 1 pharmacokinetic study of oral NEPA, the fixed combination of netupitant and palonosetron, in Chinese healthy volunteers.

Purpose: Oral NEPA, the only fixed-combination antiemetic, is composed of the neurokinin-1 receptor antagonist netupitant (300 mg) and the 5-hydroxytryptamine-3 receptor antagonist palonosetron (0.50 mg). This study was conducted to evaluate the pharmacokinetic profile of netupitant and its main metabolites M1 and M3, and palonosetron in Chinese subjects.

Efficacy of NEPA, a fixed antiemetic combination of netupitant and palonosetron, vs a 3-day aprepitant regimen for prevention of chemotherapy-induced nausea and vomiting (CINV) in Chinese patients receiving highly emetogenic chemotherapy (HEC) in a randomized Phase 3 study.

NEPA is the only fixed combination antiemetic, comprised of an NK RA (netupitant) and a 5-HT RA (palonosetron). In the first head-to-head trial to compare NK RA-containing regimens, a single oral dose of NEPA was non-inferior to a 3-day aprepitant/granisetron (APR/GRAN) regimen for the primary endpoint of overall (0-120 hours) complete response (no emesis/no rescue). This pre-specified analysis evaluates the efficacy of NEPA versus APR/GRAN in the subset of Chinese patients in the study.

Evaluation of the effect of food and age on the pharmacokinetics of oral netupitant and palonosetron in healthy subjects: A randomized, open-label, crossover phase 1 study.

Antiemetic treatment compliance is important to prevent chemotherapy-induced nausea and vomiting, a feared chemotherapy side effect. NEPA, a new oral fixed combination of netupitant, a highly selective NK1 receptor antagonist (RA), and palonosetron, a second-generation 5-HT3 RA, targets dual antiemetic pathways with a single dose. This study investigated the effect of food intake and age on NEPA pharmacokinetics (PK) and safety.

Drug-drug interaction profile of components of a fixed combination of netupitant and palonosetron: Review of clinical data.

Neurokinin-1 (NK1) receptor antagonists (RAs) are commonly coadministered with serotonin (5-HT3) RAs (e.g. palonosetron (PALO)) to prevent chemotherapy-induced nausea/vomiting.

Netupitant PET imaging and ADME studies in humans.

Netupitant is a new, selective NK1 receptor antagonist under development for the prevention of chemotherapy-induced nausea and vomiting. Two studies were conducted to evaluate the brain receptor occupancy (RO) and disposition (ADME) of netupitant in humans. Positron emission tomography (PET) imaging with the NK1 receptor-binding-selective tracer [(11) C]-GR205171 was used to evaluate the brain penetration of different doses of netupitant (100, 300, and 450 mg) and to determine the NK1 -RO duration.

Effect of netupitant, a highly selective NK₁ receptor antagonist, on the pharmacokinetics of palonosetron and impact of the fixed dose combination of netupitant and palonosetron when coadministered with ketoconazole, rifampicin, and oral contraceptives.

Objectives: Neurokinin-1 receptor antagonists (NK1 RAs) are commonly coadministered with a 5-HT3 RA such as palonosetron to prevent nausea and vomiting induced by chemotherapy. Netupitant, a new highly selective NK1 RA, is both a substrate for and a moderate inhibitor of CYP3A4. Three studies were designed to evaluate the potential drug-drug interaction of netupitant with palonosetron and of the fixed dose combination of netupitant and palonosetron, NEPA, with an inhibitor (ketoconazole), an inducer (rifampicin) and a substrate (oral contraceptives) of CYP3A4.

Effect of netupitant, a highly selective NK₁ receptor antagonist, on the pharmacokinetics of midazolam, erythromycin, and dexamethasone.

Purpose: Netupitant is a new highly selective neurokinin-1 receptor antagonist being studied for the prevention of nausea and vomiting in patients undergoing chemotherapy. In vitro studies suggest that netupitant inhibits the cytochrome P-450 isoenzyme 3A4 (CYP3A4). Because netupitant may be used with a variety of drugs, which may be substrates of CYP3A4, two studies were designed to establish the potential risk for drug-drug interaction with three different CYP3A4 substrates: midazolam, erythromycin, and dexamethasone.