The pharmacokinetics of atracurium isomers in vitro and in humans.

Abstract

Atracurium is a mixture of ten isomers. By high-performance liquid chromatography, using acidified methanol as the mobile phase and silica support, it was separated into its three geometrical isomer groups, cis-cis, cis-trans, and trans-trans, which contain three, four, and three isomers, respectively. The clinically available form of atracurium was made up of 58% cis-cis, 36% cis-trans, and 6% trans-trans isomers. In buffered saline, pH 7.4, at 37 degrees C, the half-lives of the three isomer groups were 57.1 +/- 0.9, 59.7 +/- 0.9, and 66.4 +/- 2.7 min, respectively, for the cis-cis, cis-trans, and trans-trans groups. In whole blood, under similar conditions, the three groups showed different behavior. The cis-cis group broke down in a monoexponential manner with a half-life of 23.3 +/- 2.8 min. The cis-trans group showed bi-exponential breakdown with a rapid phase of 2.3 +/- 0.4 min and a slow phase of 22.1 +/- 2.9 min. The trans-trans group decayed rapidly, but, because of the low concentration of this group in the mixture, kinetic parameters could not be obtained. In eight patients, the mean elimination half-life and apparent clearance of the cis-cis group were 20.6 +/- 1.5 min and 5.3 +/- 0.4 ml.kg-1.min-1, respectively. For the cis-trans group, the apparent elimination half-life and clearance were 17.7 +/- 1.8 min and 9.0 +/- 1.0 ml.kg-1.min-1, but these figures require care in interpretation, as this isomer group contains isomers of widely varying rates of decomposition.(ABSTRACT TRUNCATED AT 250 WORDS)