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Population pharmacokinetic model of free and total ropivacaine after transversus abdominis plane nerve block in patients undergoing liver resection
Author(s) -
Ollier Edouard,
Heritier Fabrice,
Bonnet Caroline,
Hodin Sophie,
Beauchesne Brigitte,
Molliex Serge,
Delavenne Xavier
Publication year - 2015
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/bcp.12582
Subject(s) - ropivacaine , pharmacokinetics , medicine , volume of distribution , nonmem , anesthesia , population , urology , surgery , environmental health
Aims 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.