KINETICS OF BUPIVACAINE AFTER CLONIDINE PRETREATMENT IN MICE

被引:10
作者
BRUGUEROLLE, B
ATTOLINI, L
LOREC, AM
GANTENBEIN, M
机构
[1] Faculté de Médecine de Marseille, Laboratoire de Pharmacologie Médicate, Marseille cedex 5, F 13385
来源
CANADIAN JOURNAL OF ANAESTHESIA-JOURNAL CANADIEN D ANESTHESIE | 1995年 / 42卷 / 05期
关键词
ANESTHETICS; LOCAL; BUPIVACAINE; PHARMACOLOGY; PHARMACOKINETICS; CLONIDINE; SYMPATHETIC NERVOUS SYSTEM;
D O I
10.1007/BF03015492
中图分类号
R614 [麻醉学];
学科分类号
100217 ;
摘要
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 mu g . ml(-1) versus 0.962 +/- 0.141 mu g . ml(-1) for Groups 2 and I, respectively, P = 0.01) and the area under the concentration curve (AUG, 3.530 +/- 0.330 mu g . ml(-1). hr(-1) versus 1.755 +/- 0.252 mu g . ml(-1). hr(-1) for Groups 2 and I, respectively, P < 0.01) of bupivacaine were higher in clonidine pretreated mice while the Clearance (CI) was decreased in clonidine pretreated animals (0.603 +/- 0.054 mu g . ml(-1) versus 1.264 +/- 0.447 mu g . ml(-1) for Groups 2 and 2, 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 I, 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.
引用
收藏
页码:434 / 437
页数:4
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