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A comparison of the infusion pharmacokinetics and pharmacodynamics of cisatracurium, the 1R‐ cis 1′R‐ cis isomer of atracurium, with atracurium besylate in healthy patients
Author(s) -
Smith C. E.,
Van Miert M. M.,
Parker C. J. R.,
Hunter J. M.
Publication year - 1997
Publication title -
anaesthesia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.839
H-Index - 117
eISSN - 1365-2044
pISSN - 0003-2409
DOI - 10.1111/j.1365-2044.1997.195-az0331.x
Subject(s) - medicine , pharmacodynamics , pharmacokinetics , anesthesia , atracurium besilate , pharmacology , neuromuscular blockade
We have compared the pharmacokinetics of cisatracurium with atracurium when given by bolus dose followed by continuous infusion. Twenty healthy patients were anaesthetised with thiopentone, midazolam, fentanyl and 70% nitrous oxide in oxygen. Ten patients (Group C) were randomly allocated to receive cisatracurium 0.1 mgkg −1 and 10 patients (Group A) were given atracurium 0.5 mgkg −1 . Neuromuscular block was monitored using a mechanomyograph. When the first twitch of the train‐of‐four had recovered to 5% of control, an infusion of cisatracurium 3 μgkg −1 .min −1 was started in Group C and an infusion of atracurium 10 μgkg −1 .min −1 was started in Group A. The infusion rates were adjusted to maintain the first twitch of the train‐of‐four at 5% of control. The times to 90% and maximum depression of the first twitch of the train‐of‐four were significantly longer after cisatracurium than atracurium (2.2 and 3.4 min compared with 1.3 and 1.8 min, respectively; p < 0.01 in each instance). No significant differences were found in recovery parameters between the two groups. Blood samples were taken at regular intervals following the bolus, during the infusion and for 8 h thereafter. The plasma samples were analysed using high‐performance liquid chromatography for cisatracurium and atracurium (using a method which distinguishes between the three geometric isomer groups), laudanosine and monoquaternary alcohol. The results were analysed using the Non‐linear Mixed Effects Model program. A two‐compartment model was fitted to the data. The different isomer groups of atracurium have different pharmacokinetics, the trans–trans group having the highest clearance (1440 mlmin −1 ) and the cis–cis group the lowest (499 mlmin −1 ). The clearance of cisatracurium (425 mlmin −1 ) is less than that of cis–cis atracurium and its elimination half‐life is longer (34.9 min and 21.9 min, respectively). The plasma concentration of laudanosine after cisatracurium was one‐fifth of that after atracurium.