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Canadian Journal of Anesthesia, Vol 42, 434-437, Copyright © 1995 by Canadian Anesthesiologists' Society

ARTICLES

Kinetics of bupivacaine after clonidine pretreatment in mice

B Bruguerolle, L Attolini, AM Lorec and M Gantenbein
Laboratoire de Pharmacologie Medicale, Faculte de Medecine de Marseille, France.

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.


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S. Inomata, E. Tanaka, M. Miyabe, Y. Kakiuchi, A. Nagashima, Y. Yamasaki, S. Nakayama, Y. Baba, H. Toyooka, K. Okuyama, et al.
Plasma Lidocaine Concentrations During Continuous Thoracic Epidural Anesthesia After Clonidine Premedication in Children
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