The Pharmacokinetics of Atracurium Isomers In Vitro and in Humans

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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.degree. 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 .cntdot. kg-1 .cntdot. 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 .cntdot. kg-1 .cntdot. min-1, but these figures require care in interpretation, as this isomer group contains isomers of widely varying rates of decomposition. Quantitative pharmacokinetic data for the trans-trans group could not be obtained. The short half-life isomers of atracurium could be of practical usefulness in the future.

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