In vitro degradation of atracurium and cisatracurium at pH 7.4 and 37 degrees C depends on the composition of the incubating solutions.
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 Sörensen (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.
Weindlmayr-Goettel
M
M
Department (B) of Anaesthesiology and General Intensive Care, University of Vienna, Austria.
Kress
H G
HG
Hammerschmidt
F
F
Nigrovic
V
V
D001279:Atracurium / Q000737:chemistry*; D002021:Buffers; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008956:Models, Chemical; D003473:Neuromuscular Nondepolarizing Agents / Q000737:chemistry*; D013237:Stereoisomerism; D013696:Temperature
D002021:Buffers; D003473:Neuromuscular Nondepolarizing Agents; D001279:Atracurium