Riff Camille, Bourgoin Aurélie, Marsot Amelie, Allanioux Laurent, Leone Marc, Blin Olivier, Guilhaumou Romain
Service de Pharmacologie Clinique et Pharmacovigilance, Hôpital de la Timone, AP-HM, 13385, Marseille, France.
Pharmacologie Intégrée et Interface Clinique Industrielle, Institut des Neurosciences Timone - AMU-CNRS 7289, Aix-Marseille Université, 13385, Marseille, France.
Eur J Clin Pharmacol. 2018 Oct;74(10):1309-1315. doi: 10.1007/s00228-018-2503-8. Epub 2018 Jun 16.
Tumescent lidocaine anesthesia (TLA) is an opportunity to perform mastectomy for breast cancer without general anesthesia in elderly women. Few reports are available on the pharmacokinetics of lidocaine in a context of TLA during a unilateral mastectomy. The aim of this study was to describe lidocaine pharmacokinetics in elderly women undergoing breast cancer surgery after TLA and to explore the risk of the toxicity of this technique.
A prospective study was conducted to examine the pharmacokinetics of lidocaine in women undergoing TLA. TLA consists of an intradermal lidocaine instillation (20 mL, 1% [200 mg]) followed by a tumescent lidocaine infiltration (100 mL of 1% lidocaine [1000 mg] and 0.5 mg epinephrine to 1 L Ringer's lactate) via an infusion pump. A population pharmacokinetic (popPK) analysis was performed using the nonlinear mixed effects model (NONMEM).
The analysis included 116 observations from 17 women with a median (range) age of 83.4 (60.5-90.0). The median tumescent lidocaine dose was 800 mg (range 375-1000 mg) infused over 48.0 ± 11.0 min. A one-compartment disposition model with first order absorption, two input compartments, and a central elimination best described the pharmacokinetics of lidocaine. The estimates (between subject variability; relative standard error, %) of apparent volume, apparent clearance, tumescent absorption rate, and instillation absorption rate were 195.0 (46.3; 14.5%) L, 24.7 (48.9; 13.3%) L h, 0.28 (39.6; 13.8%) h, and 2.56 (135.3; 44.9%) h, respectively.
This is the first popPK model developed to describe kinetic profiles of TLA. These findings confirm the slow diffusion of lidocaine from the tumescent deposit.
肿胀麻醉利多卡因麻醉（TLA）为老年女性乳腺癌患者在不进行全身麻醉的情况下实施乳房切除术提供了机会。关于单侧乳房切除术中TLA情况下利多卡因的药代动力学的报道较少。本研究的目的是描述TLA后接受乳腺癌手术的老年女性的利多卡因药代动力学，并探讨该技术的毒性风险。
进行了一项前瞻性研究，以检查接受TLA的女性中利多卡因的药代动力学。TLA包括皮内注射利多卡因（20 mL，1%[200 mg]），随后通过输液泵进行肿胀麻醉利多卡因浸润（100 mL 1%利多卡因[1000 mg]和0.5 mg肾上腺素加入1 L乳酸林格氏液）。使用非线性混合效应模型（NONMEM）进行群体药代动力学（popPK）分析。
分析包括来自17名女性的116次观察结果，年龄中位数（范围）为83.4（60.5 - 90.0）岁。肿胀麻醉利多卡因的中位剂量为800 mg（范围375 - 1000 mg），在48.0±11.0分钟内输注。具有一级吸收、两个输入室和中央消除的一室处置模型最能描述利多卡因的药代动力学。表观体积、表观清除率、肿胀吸收速率和注射吸收速率的估计值（个体间变异性；相对标准误差，%）分别为195.0（46.3；14.5%）L、24.7（48.9；13.3%）L/h、0.28（39.6；13.8%）h和2.56（135.3；44.9%）h。
这是第一个用于描述TLA动力学特征的popPK模型。这些发现证实了利多卡因从肿胀沉积物中缓慢扩散。
