title: Population pharmacokinetic model of free and total ropivacaine after transversus abdominis plane nerve block in patients undergoing liver resection.
abstract: OBJECTIVE
  The aim of this study was to develop a pharmacokinetic model in order to characterize the free and total ropivacaine concentrations after transversus abdominis plane block in a population of patients undergoing liver resection surgery. In particular, we evaluated the impact of the size of liver resection on ropivacaine pharmacokinetics.
  
  
  METHODS
  This work is based on a single-centre, double-blinded, randomized, placebo-controlled study. Among the 39 patients included, 19 patients were randomized to the ropivacaine group. The free and total ropivacaine concentrations were measured in nine or 10 blood samples per patient. A pharmacokinetic model was built using a nonlinear mixed-effect modelling approach.
  
  
  RESULTS
  The free ropivacaine concentrations remained under the previously published toxic threshold. A one-compartment model, including protein binding site with a first-order absorption, best described the data. The protein binding site concentration was considered as a latent variable. Bodyweight, the number of resected liver segments and postoperative fibrinogen evolution were, respectively, included in the calculation of the volume of distribution, clearance and binding site production rate. The resection of three or more liver segments was associated with a 53% decrease in the free ropivacaine clearance.
  
  
  CONCLUSIONS
  Although large liver resections were associated with lower free ropivacaine clearance, the ropivacaine pharmacokinetic profile remained within the safe range after this type of surgery.
authors.affiliation: Université Claude Bernard Lyon 1, F-69100, Villeurbanne, France.|Laboratoire de Pharmacologie Toxicologie, CHU Saint-Etienne, F-42055, Saint-Etienne, France.
authors.forename: Edouard
authors.identifier: http://orcid.org/0000-0001-6925-2941
authors.initials: E
authors.lastname: Ollier
authors.affiliation: Département d'anesthésie Réanimation, CHU de Saint-Etienne, F-42055, Saint-Etienne, France.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Heritier
authors.affiliation: Département d'anesthésie Réanimation, CHU de Saint-Etienne, F-42055, Saint-Etienne, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Bonnet
authors.affiliation: Laboratoire de Pharmacologie Toxicologie, CHU Saint-Etienne, F-42055, Saint-Etienne, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Hodin
authors.affiliation: Département d'anesthésie Réanimation, CHU de Saint-Etienne, F-42055, Saint-Etienne, France.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Beauchesne
authors.affiliation: Département d'anesthésie Réanimation, CHU de Saint-Etienne, F-42055, Saint-Etienne, France.|Université Jean Monnet, Université de Lyon, F-42023, Saint-Etienne, France.
authors.forename: Serge
authors.initials: S
authors.lastname: Molliex
authors.affiliation: Laboratoire de Pharmacologie Toxicologie, CHU Saint-Etienne, F-42055, Saint-Etienne, France.|Université Jean Monnet, Université de Lyon, F-42023, Saint-Etienne, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Delavenne
mesh_terms: D000328:Adult; D000368:Aged; D000577:Amides / Q000097:blood / Q000493:pharmacokinetics*; D000779:Anesthetics, Local / Q000097:blood / Q000493:pharmacokinetics; D004311:Double-Blind Method; D006801:Humans; D008099:Liver / Q000601:surgery*; D008875:Middle Aged; D008954:Models, Biological; D009407:Nerve Block / Q000379:methods*; D000077212:Ropivacaine
chemical_list: D000577:Amides; D000779:Anesthetics, Local; D000077212:Ropivacaine
keywords: liver resection; model; population pharmacokinetics; protein binding; ropivacaine; transversus abdominis plane block