Ropivacaine Wound Infiltration for Pain Management After Breast Cancer Mastectomy: A Population Pharmacokinetic Analysis. Issue 8 (16th April 2018)

• Record Type: Journal Article
• Authors: Riff, Camille; Guilhaumou, Romain; Marsot, Amelie; Beaussier, Marc; Cohen, Monique; Blin, Olivier; Francon, Daniel
• Is Part Of: Clinical pharmacology in drug development. Volume 7:Issue 8(2018)
• Page Start: 811
• Page End: 819
• Publication Date: 2018-04-16
• Subjects: mastectomy -- nonlinear models -- pharmacokinetics -- ropivacaine; Drugs -- Testing -- Periodicals; Drug development -- Periodicals; Clinical pharmacology -- Periodicals; 615.580724
• DOI: 10.1002/cpdd.452
• Languages: English
• ISSNs: 2160-7648

Abstract

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 75 hours. Women undergoing a unilateral mastectomy were scheduled to receive CWI for 40 hours for postoperative analgesia. A 10‐mL ropivacaine 0.75% bolus followed by continuous infusion (400 mL of 0.2% ropivacaine at a flow rate of 10 mL/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) 0.406 h ‐1 . The model predicted Cmax as 1.45 ± 0.80 μg/mL, which occurred in the 42.4 th hour (39–45.9 hours). This popPK model describes the pharmacokinetics of ropivacaine during continuous wound infusion and confirms the safety profile of the present technique.