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A4139
October 27, 2015
1:00:00 PM - 3:00:00 PM
Room Hall B2-Area E
A Population Pharmacokinetics of Intravenous Ramosetron, 5-HT3 Receptor Antagonist
SeongWook Jeong, M.D.,Ph.D., Seong-Heon Lee, M.D.,Ph.D., Jia Song, M.D., Injae Kim, Student, Jeong-Il Choi, M.D.,Ph.D., Woong Mo Kim, M.D.,Ph.D., Hyung Gon Lee, M.D.,Ph.D., Myung Ha Yoon, M.D.,Ph.D.
Chonnam University Hwasun Hospital, Hwasun, Korea, Republic of
Disclosures: S. Jeong: None. S. Lee: None. J. Song: None. I. Kim: None. J. Choi: None. W. Kim: None. H. Lee: None. M. Yoon: None.
Background: Ramosetron is a potent, highly selective 5-hydroxy-tryptamine receptor 3 antagonist being used to prevent and treat postoperative nausea and vomiting (PONV) and chemotherapy-induced nausea and vomiting (CINV). The prophylactic failure of PONV/CINV sometimes occurs, and the pharmacokinetic inter-individual variability can be one of the possible causes of the failure. The present study was designed to construct a population pharmacokinetic model of ramosetron and to evaluate significant covariates affecting ramosetron pharmacokinetics in patients undergoing surgery and chemotherapy.

Methods: Patients aged 19-80 years received one of a bolus dosages of ramosetron (0.3 mg, 0.45 mg or 0.6 mg) intravenously 30 min before the end of surgery or the administration of chemotherapeutic agent. Blood samples were collected and plasma concentrations of ramosetron were measured by high performance liquid chromatography-tandem mass spectrometry. Pooled data from 50 surgical patients and 50 oncology patients including 651 pharmacokinetic samples, were used for population pharmacokinetic analysis using the nonlinear mixed effect modelling program (NONMEM®).

Results: Ramosetron pharmacokinetics was best described by a three-compartment mammillary model with first-order elimination. A covariate analysis identified that ideal body weight (IBW) and lean body mass (LBM) had a positive relationship with clearance and volume of a peripheral compartment (V2), respectively. The results of the final model were as follows: 0.22 + (IBW - 57) × 0.0043 L/min (CL), 0.75 L/min (Q2), 1.83 L/min (Q3), 5.14 L (V1), 89.2 + (LBM - 42) × 2.13 L (V2), 20 L (V3). The bootstrap method and visual predictive check showed that the final pharmacokinetic model was appropriate.

Conclusions: Population pharmacokinetic model of ramosetron was constructed in surgical and oncology patients, with individualization of pharmacokinetic parameters based on IBW and LBM. This analysis could provide framework for the potential dosing modification of the ramosetron prophylaxis.

Copyright © 2015 American Society of Anesthesiologists