British Journal of Anaesthesia, Vol 75, Issue 4 431-435, Copyright © 1995 by The Board of Management and Trustees of the British Journal of Anaesthesia
N. B. Eastwood, A. H. Boyd, CJR. Parker and J. M. Hunter
To ascertain the effects of chronic renal failure on the pharmacokinetics
of 1R-cis 1'R-cis atracurium besylate (a stereoisomer, designated 51W89),
we gave a bolus dose of 0.1 mg kg-1 (2 x ED95) to 17 patients with
end-stage renal failure and to 15 patients with normal renal function
undergoing elective surgery. All patients received thiopentone, fentanyl
and midazolam i.v. and 70% nitrous oxide in oxygen. Blood samples were
obtained over 8 h and plasma analysed for 51W89 and laudanosine
concentration, using high pressure liquid chromatography. A two-compartment
model was fitted to the 51W89 plasma concentration data using the NONMEM
program, to estimate pharmacokinetic variables and to determine the
influence of renal failure, age, weight and sex. Clearance of 51W89 was
found to be reduced by 13% in renal failure. The typical value of T1/2 beta
was 4.2 min longer in renal failure than in the healthy patients (34.2 vs
30.0 min, P < 0.005). In the healthy patients, clearance of 51W89 was
greater in males, but it decreased with increasing age by approximately 1.5
ml min-1 yr-1. Mean plasma laudanosine concentrations were significantly
higher in the renal failure group; nevertheless, they were approximately
one-tenth of those reported after atracurium.
CLINICAL INVESTIGATIONS
Pharmacokinetics of 1R-cis 1'R-cis atracurium besylate (51W89) and plasma laudanosine concentrations in health and chronic renal failure
University Department of Anaesthesia, Royal Liverpool University Hospital, Prescot Street, Liverpool L69 3BX
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