可乐定预处理后小鼠体内布比卡因的动力学

Kinetics of bupivacaine after clonidine pretreatment in mice.

作者信息

Bruguerolle B, Attolini L, Lorec A M, Gantenbein M

机构信息

Laboratoire de Pharmacologie Médicale, Faculté de Médecine de Marseille, France.

出版信息

Can J Anaesth. 1995 May;42(5 Pt 1):434-7. doi: 10.1007/BF03015492.

DOI:10.1007/BF03015492

PMID:7614654

Abstract

Previous studies have reported that clonidine pretreatment causes an increase in the local anaesthetic activity of bupivacaine. This study was designed to document possible changes in the pharmacokinetic behaviour of bupivacaine and its main metabolite, desbutylbupivacaine, PPX, in mice after a single, 0.1 mg.kg-1, injection of clonidine. Kinetic variables of bupivacaine were determined after a single 20 mg.kg-1 ip dose of bupivacaine in controls (Group I) and in clonidine (0.1 mg.kg-1 ip) pretreated mice (Group 2). The maximal concentration in serum (Cmax, 2.553 +/- 0.862 micrograms.ml-1 versus 0.962 +/- 0.141 microgram.ml01 for Groups 2 and 1, respectively, P = 0.01) and the area under the concentration curve (AUC, 3.530 +/- 0.330 micrograms.ml-1.hr-1 versus 1.755 +/- 0.252 micrograms.ml-1.hr-1 for Groups 2 and 1, respectively, P < 0.01) of bupivacaine were higher in clonidine pretreated mice while the Clearance (Cl) was decreased in clonidine pretreated animals (0.603 +/- 0.054 micrograms.ml-1 versus 1.264 +/- 0.447 micrograms.ml-1 for Groups 2 and 1, respectively, P < 0.01). The ratio of AUC PPX/AUC bupivacaine (which may partially indicate the rate of metabolism) was lower in presence of clonidine (0.220 +/- 0.019 against 0.425 +/- 0.033 for Groups 2 and 1, respectively, P < 0.01). Our data indicate decreased metabolism in the clonidine-treated mice which suggests altered hepatic metabolism of bupivacaine by clonidine. This may explain the previously reported enhanced anaesthetic activity of bupivacaine in the presence of clonidine.

摘要

先前的研究报道，可乐定预处理会使布比卡因的局部麻醉活性增强。本研究旨在记录单次注射0.1mg·kg⁻¹可乐定后，小鼠体内布比卡因及其主要代谢产物去丁基布比卡因（PPX）药代动力学行为的可能变化。在对照组（第一组）和可乐定（0.1mg·kg⁻¹腹腔注射）预处理的小鼠（第二组）中，单次腹腔注射20mg·kg⁻¹布比卡因后，测定布比卡因的动力学变量。布比卡因的血清最大浓度（Cmax，第二组和第一组分别为2.553±0.862μg·ml⁻¹和0.962±0.141μg·ml⁻¹，P = 0.01）以及浓度曲线下面积（AUC，第二组和第一组分别为3.530±0.330μg·ml⁻¹·hr⁻¹和1.755±0.252μg·ml⁻¹·hr⁻¹，P < 0.01）在可乐定预处理的小鼠中较高，而可乐定预处理动物的清除率（Cl）降低（第二组和第一组分别为0.603±0.054μg·ml⁻¹和1.264±0.447μg·ml⁻¹，P < 0.01）。可乐定存在时，AUC PPX/AUC布比卡因的比值（这可能部分表明代谢速率）较低（第二组和第一组分别为0.220±0.019和0.425±0.033，P < 0.01）。我们的数据表明可乐定处理的小鼠代谢降低，这表明可乐定改变了布比卡因的肝脏代谢。这可能解释了先前报道的在可乐定存在时布比卡因麻醉活性增强的现象。