Ropivacaine Wound Infiltration for Pain Management After Breast Cancer Mastectomy: A Population Pharmacokinetic Analysis

Abstract

Ropivacaine continuous wound infusions (CWIs) are extensively used as a component of multimodal analgesia. The rational application of CWI of ropivacaine requires a thorough understanding of its pharmacokinetics to investigate the risk of potential systemic toxicity. A population pharmacokinetic (popPK) study was undertaken to describe the pharmacokinetics of ropivacaine CWI during 75hours. Women undergoing a unilateral mastectomy were scheduled to receive CWI for 40hours for postoperative analgesia. A 10-mL ropivacaine 0.75% bolus followed by continuous infusion (400mL of 0.2% ropivacaine at a flow rate of 10mL/h) was administered via a multihole catheter placed on the major pectoral muscle. PopPK analysis was performed using the nonlinear mixed-effects model. A 1-compartment disposition model with an absorption compartment and a transit compartment for the infusion best describes the data (67 observations from 10 women). Population parameter estimates (between-subject variability, %) are apparent central volume (V/F) 269 L (39.1%), apparent clearance (CL/F) 18.8 h-1 (74.9%), and absorption rate (K12) 0.406h-1 . The model predicted Cmax as 1.45±0.80μg/mL, which occurred in the 42.4th hour (39-45.9hours). This popPK model describes the pharmacokinetics of ropivacaine during continuous wound infusion and confirms the safety profile of the present technique.