Ollier Edouard, Heritier Fabrice, Bonnet Caroline, Hodin Sophie, Beauchesne Brigitte, Molliex Serge, Delavenne Xavier
Université Claude Bernard Lyon 1, F-69100, Villeurbanne, France.
Laboratoire de Pharmacologie Toxicologie, CHU Saint-Etienne, F-42055, Saint-Etienne, France.
Br J Clin Pharmacol. 2015 Jul;80(1):67-74. doi: 10.1111/bcp.12582. Epub 2015 May 28.
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.
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.
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.
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.
本研究旨在建立一个药代动力学模型，以描述肝切除手术患者群体中腹横肌平面阻滞术后罗哌卡因的游离浓度和总浓度。特别是，我们评估了肝切除大小对罗哌卡因药代动力学的影响。
本研究基于一项单中心、双盲、随机、安慰剂对照试验。在纳入的39例患者中，19例患者被随机分配至罗哌卡因组。每位患者采集9或10份血样，测定罗哌卡因的游离浓度和总浓度。采用非线性混合效应建模方法建立药代动力学模型。
罗哌卡因游离浓度维持在先前公布的中毒阈值以下。一个包括具有一级吸收的蛋白质结合位点的单室模型能最好地描述数据。蛋白质结合位点浓度被视为一个潜在变量。体重、切除的肝段数量和术后纤维蛋白原变化分别纳入分布容积、清除率和结合位点产生率的计算。切除三个或更多肝段与罗哌卡因游离清除率降低53%相关。
虽然大的肝切除与罗哌卡因游离清除率降低有关，但此类手术后罗哌卡因的药代动力学特征仍在安全范围内。
