Pharmacokinetics (PK) and Safety Evaluation of Palonosetron (PALO) Administered as a 15-minute Infusion Versus a 30-second Infusion in Healthy Subjects

20700 (25%) and 20700 (21%) ng·hr/L, respectively. The ratio of geometric means (90% CI) of Treatment A to B for Cmax was 60.2% (40.4% - 89.8%) and for AUC(0-¥) was 99.3% (91.9 - 107.3). Mean (CV) values of CLp, Vdss and T1/2 for Treatments A and B were 214 (26%) and 209 (21%) ml/min; 611 (24%) and 554 (30%), and 37.0 (24%) and 33.3 (30%) hr for treatment A and B, respectively. CLp (p=0.711), Vdss (p=0.260), and T1/2 (p=0.283) were not significantly different for the treatments. PALO was well tolerated,no significant change in vital signs, ECGs,no clinically important drug-related adverse events. The alternative administration of PALO given as a 15-minute IV infusion was safe and well tolerated, with a predictable PK profile that resulted in equivalent AUC(0-¥) and lower Cmax compared to a 30-second infusion. Palonosetron (Aloxi®) sNovel second-generation pharmacologically distinct 5-HT3 receptor antagonist sAt least 30-fold higher binding affinity for the 5-HT3 receptor compared with other agents in the class1, 2 sExtended plasma elimination half-life (approximately 40 hours)3 sThe first and only 5-HT3 receptor antagonist to be indicated for the prevention of both acute and delayed CINV caused by moderately emetogenic chemotherapy based on superior clinical efficacy3-5 sAlso indicated for the prevention of acute CINV caused by highly emetogenic chemotherapy3 sExhibits dual routes of elimination (renal and hepatic) and multiple CYP450 isozymes are involved in its metabolism (primarily CYP2D6 with minor contribution of CYP3A and CYP1A2)3. Low potential for drug-drug interactions. No dose reduction required for renal or hepatic impairment3