Safety and Pharmacokinetic Evaluation of Palonosetron Given on Day 1 and 3 for Patients Who are to Receive a High or Moderate Risk of Chemotherapy-Induced Nausea and Vomiting (CINV)

ABSTRACT Aim To assess safety, pharmacokinetics and tolerability of repeated dosing of palonosetron in patients receiving chemotherapy categorized as having a high or moderate emetic risk. Method Nineteen patients undergoing high or moderate emetic risk for CINV were given palonosetron 0.75mg intravenously once daily for 30 min on day 1 and 3. Blood samples for the first 6 patients were obtained for pharmacokinetics analysis from day 1 through 5. To evaluate safety profiles, serial complete blood cell counts, blood chemistry tests and electrocardiograms were also performed. Result The pharmacokinetic studies of 6 patients showed mean Cmax values on day1 and 3 were 2.05 and 2.90ng/mL, respectively, with coefficients of variation (CV) of 30.9% and 34.2%. Mean AUC0-48hr values were 42.4 and 58.3 ng•hr/mL on day1 and 3, with a CV of 21.2% and 23.2%, respectively. T1/2 of palonosetron was approximately 40 hours and was constant in day1 and 3. Accumulation of palonosetron on day3 was 1.42-fold for Cmax and 1.37-fold for AUC0-48hr. Treatment-related adverse events for 19 patients including above 6 patients were constipation and loss of appetite which might be secondary to antineoplastic agents, but were mild and transient. Complete response defined by no emesis and no rescue antiemetics was 100% for acute and 73% for delayed CINV, respectively. Conclusions Repeated dosing of palonosetron on day1 and 3 was safe and well tolerated in patients who received high to moderate emetic risk chemotherapy. Disclosure All authors have declared no conflicts of interest.