Skip Navigation

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow E-Letters: Submit a response to the article
Right arrow Alert me when this article is cited
Right arrow Alert me when E-letters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (1)
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Laurin, J.
Right arrow Articles by Varin, F.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Laurin, J.
Right arrow Articles by Varin, F.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

British Journal of Anaesthesia, 2002, Vol. 89, No. 6 832-838
© 2002 The Board of Management and Trustees of the British Journal of Anaesthesia

Clinical Investigations

Stereoselective in vitro degradation pattern of mivacurium in human plasma{dagger}

J. Laurin1, F. Donati2 and F. Varin*,1

1 Faculté de Pharmacie, Université de Montréal C.P. 6128, Succ. Centre-Ville, Montréal (QC), Canada H3C 3J7. 2 Département d’Anesthésie, Faculté de Médecine, Université de Montréal C.P. 6128, Succ. Centre-Ville, Montréal (QC), Canada H3C 3J7 france.varin@umontreal.ca


{dagger}This research was supported by the Canadian Institutes of Health Research (MA-10274). A CIHR-Rx&D studentship was awarded to Julie Laurin.

Background. Mivacurium is a mixture of three isomers, two of which are rapidly broken down in vivo by plasma cholinesterases. This study investigates the stereospecificity of mivacurium in vitro degradation to determine if it accounts for its in vivo behaviour.

Methods. The in vitro rate of degradation of each isomer of mivacurium and the in vitro rate of formation of their primary (monoesters and alcohols) and secondary (alcohols) metabolites were examined using human plasma from six healthy volunteers. The in vitro rate of degradation of the monoester metabolites was also assessed. All these determinations were made using a stereospecific high-performance liquid chromatography assay.

Results. The in vitro rate of disappearance of the two active isomers of mivacurium was very rapid, with mean values for the trans trans and cis trans isomers of 0.803 and 0.921 min–1 respectively. These values are twofold faster than published in vivo data. The in vitro rate of disappearance was much slower for the cis cis isomer, with a mean value of 0.0106 min–1. The cis trans isomer was converted exclusively to cis monoester and trans alcohol, while only metabolites in the trans and cis configuration were found for the trans trans and cis cis isomers respectively. Mean in vitro rates of disappearance for the trans and cis monoester were 0.00750 and 0.000633 min–1 respectively.

Conclusions. The in vitro rates of hydrolysis of the active isomers of mivacurium confirm that plasma cholinesterases play a major role in their in vivo degradation, but that in vivo elimination is slowed by extravascular distribution. Mivacurium hydrolysis is stereoselective, the ester group in the trans configuration being more accessible to enzymatic attack. This stereoselective pattern, along with the relatively slow breakdown of the cis cis isomer, sheds light on the in vivo disposition of the cis alcohol metabolite.

Br J Anaesth 2002; 89: 832–8


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.