Pharmacokinetic and pharmacodynamic study of ramosetron to prevent chemotherapy-induced nausea and vomiting.

e20650 Background: Chemotherapy induced nausea and vomiting (CINV) is one of the most concerning adverse effects from cytotoxic chemotherapy. Despite appropriate use of antiemetic guidelines, 20-30 % of patients experience breakthrough nausea and vomiting secondary to chemotherapy. This study was prospectively conducted to determine the optimal concentration of ramosetron to prevent CINV based on pharmacokinetics (PK) and pharmacodynamics (PD) using Rhodes index (RI) as a clinical parameter. Methods: Patients who treated FOLFOX adjuvant chemotherapy after colon cancer surgery were randomized into three groups following as ramosetron 0.3mg (standard dose), 0.45mg and 0.6mg intravenously before chemotherapy. Plasma concentration of ramosetron was measured at 10min, 1hr, 6hrs, 24hrs and 48hrs and patients were evaluated the Rhodes Index of nausea, vomiting and retching (RINVR) to grade CINV at each time. Results: Fifty-one patients were enrolled in this study and one patient decided to refuse, so data from fifty patients were analyzed. The serious AE was not shown according to dose escalation. PK parameters were approximately dose-proportional (Table). In correlation analysis, AUClast is significantly associated with dose escalation (p=0.022) and it trends to reverse correlation to RINVR (p=0.061) according to dose level. When the patients divided into two groups based on median AUClast, patients in higher level of AUClast showed significantly improved RINVR score than lower level of AUClast (p=0.048). Conclusions: Ramosetron showed generally dose-proportional PK parameters and this study suggested that higher dose of ramosetron could be used to improve CINV in subsequent cycle of chemotherapy. Also RINVR is important tool for assessing of CINV to predict optimal antiemetic use, therefore individual approach for managing of CINV is needed. 0.3mg (N=17) 0.45mg (N=15) 0.6mg (N=18) Tmax(h) 0.17 0.17 0.17 Cmax(ng/ml) 3.2±0.98 4.9±2.19 7.3±4.43 AUClast(ng.h/ml) 16.5±5.1 23.0±8.95 28.1±10.23