Palonosetron is used to prevent and treat chemotherapy-induced nausea and vomiting (CINV). It is a 5-HT3 antagonist.
Palonosetron is administered intravenously or as a single oral capsule. It has a longer duration of action than other 5-HT3 antagonists. The oral formulation was approved on August 22, 2008, for the prevention of acute CINV alone, as a large clinical trial did not show oral administration to be as effective as intravenous use against delayed CINV. It is on the World Health Organization’s List of Essential Medicines.
Structure:
Physicochemical Data:
IUPAC Name | (3aS)-2-[(3S)-1-Azabicyclo[2.2.2]oct-3-yl]-2,3,3a,4,5,6-hexahydro-1H-benz[de]isoquinolin-1-one |
CAS Number | 135729-61-2 |
Molecular Formula | C19H24N2O |
Molecular Mass | 296.414 g·mol−1 |
Melting Point | |
Density |
Pharmacokinetic Data:
Absorption | Low oral bioavailability. |
Volume of Distribution | 8.3 ± 2.5 L/kg |
Protein Binding | 62% |
Metabolism | Hepatic (50%), primarily CYP2D6-mediated, although CYP3A4 and CYP1A2 are also involved. |
Route of Elimination | After a single intravenous dose of 10 mcg/kg [14C]-palonosetron, approximately 80% of the dose was recovered within 144 hours in the urine. |
Half-life | Approximately 40 hours. |
Clearance | 160 +/- 35 mL/h/kg |
Toxicity | A single intravenous dose of palonosetron at 30 mg/kg (947 and 474 times the human dose for rats and mice, respectively, based on body surface area) was lethal to rats and mice. The significant signs of toxicity were convulsions, gasping, pallor, cyanosis, and collapse. |
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