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British Journal of Anaesthesia, Vol 81, Issue 3 409-414, Copyright © 1998 by The Board of Management and Trustees of the British Journal of Anaesthesia

LABORATORY INVESTIGATIONS

In vitro degradation of atracurium and cisatracurium at pH 7.4 and 37 degrees C depends on the composition of the incubating solutions

M. Weindlmayr-Goettel, H. G. Kress, F. Hammerschmidt and V. Nigrovic
Department (B) of Anaesthesiology and General Intensive Care, University of Vienna, Vienna, Austria and Ludwig Boltzmann Institute of Experimental Anaesthesiology and Research in Intensive Care Medicine, Vienna, Austria; Institute of Organic Chemistry, University of Vienna, Vienna, Austria; Department of Anesthesiology and Pharmacology, Medical College of Ohio, Toledo, OH, USA

The pharmacokinetic models proposed for atracurium or cisatracurium are based on the assumption that spontaneous degradation via Hofmann elimination proceeds in vivo at the same rate as measured in vitro at pH 7.4 and 37 degrees C. As different degradation rates have been reported for all 10 stereoisomers of atracurium measured together, for each of its three isomeric groups, and for the single isomer cisatracurium, we studied if the rate is dependent on factors other than pH and temperature. In vitro degradation of atracurium and cisatracurium was studied at 37 degrees C and pH 7.4 in nine incubating solutions containing one of three buffer systems (phosphate, HEPES or Tris) and additives (sodium chloride, potassium sulphate or glucose). Concentrations of atracurium, cisatracurium and laudanosine were measured after incubation for up to 240 min using an HPLC method. Degradation of atracurium proceeded monoexponentially. The rate was slower in the presence of sodium chloride, potassium sulphate, and in a lower concentration of the phosphate buffer. Glucose enhanced the degradation. At the same total buffer concentration (50 mmol litre-1), degradation was fastest in the phosphate, intermediate in the HEPES and slowest in the Tris buffer. Degradation rates of cisatracurium in sodium phosphate 50 mmol litre-1 and Sorensen (Na-K phosphate) buffer 66.7 mmol litre-1 were similar to those of atracurium. We conclude that, at constant pH and temperature, the degradation rate of atracurium was dependent on the total concentration of the base in the incubating solution.
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Home page
 Br J AnaesthHome page
M. Weindlmayr-Goettel, H. Gilly, and H. G. Kress
Does ester hydrolysis change the in vitro degradation rate of cisatracurium and atracurium?
Br. J. Anaesth., April 1, 2002; 88(4): 555 - 562.
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