Published in Br J Clin Pharmacol. 2014 Dec 31
Authors: Ollier E et al
The aim of this study was to develop a pharmacokinetic model in order to characterise the free and total ropivacaine concentrations after TAP block in a population of patients undergoing liver resection surgery. In particular, we evaluated the impact of the liver resection size on ropivacaine pharmacokinetics.
This work is based on a single-centre, double-blinded, randomised, placebo-controlled study. Among the 39 patients included, 19 patients were randomised to the ropivacaine group. The free and total ropivacaine concentrations were measured in 9 to 10 blood samples per patient. A pharmacokinetic model was built using a nonlinear mixed effect modelling approach.
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. Body weight, 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.
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.