Population pharmacokinetics and prophylactic anti-emetic efficacy of ramosetron in surgical patients

Abstract

AimsThis study characterized the pharmacokinetics of ramosetron and compared prophylactic anti-emetic efficacy with that of ondansetron in a large population. MethodsFifty-eight patients consented to the pharmacokinetic analysis and were assigned randomly to receive 0.3, 0.45 or 0.6mg ramosetron after induction of anaesthesia. Blood samples were acquired at preset intervals. Non-compartmental and population pharmacokinetic analyses were performed. In total, 1102 patients consented to the evaluation of prophylactic anti-emetic efficacy and were allocated randomly to receive 0.3mg ramosetron or 4mg ondansetron at the end of surgery. An additional 16mg ondansetron were mixed in the intravenous patient-controlled analgesia pump of the ondansetron group. Post-operative nausea and vomiting (PONV) were evaluated 6, 24 and 48h post-operatively using the Rhodes index of nausea, vomiting and retching (RINVR). Administration of rescue anti-emetics and adverse events were evaluated. ResultsThe pharmacokinetic parameter estimates were V-1 (l)=5.12, V-2 (l)=108, CL (lmin(-1))=0.08+(59age(-1))x0.09, Q (lmin(-1))=1.42. The incidences of PONV in the ramosetron and ondansetron groups were 77 (13.9%) and 113 (20.6%) and 44 (7.9%) and 66 (12.0%) at 24 and 48h post-operatively, respectively (P=0.004, 0.030). RINVR was significantly lower in the ramosetron than the ondansetron group 24 and 48h post-operatively (P=0.003, 0.025). Use of rescue anti-emetics and incidence of adverse events were comparable. ConclusionsA two compartment mammillary model was used to describe ramosetron pharmacokinetics. Prophylactic anti-emetic efficacy of ramosetron was significantly better 24 and 48h post-operatively than that of ondansetron, particularly when the Apfel score was3.