British Journal of Anaesthesia, Vol 75, Issue 1 31-36, Copyright © 1995 by The Board of Management and Trustees of the British Journal of Anaesthesia
A. G. Head-Rapson, J. C. Devlin, CJR. Parker and J. M. Hunter
We have studied the pharmacokinetics of cis-trans, trans-trans and cis- cis
mivacurium in nine healthy patients (creatinine clearance 66-133 ml min-1),
in seven patients with end-stage renal failure requiring dialysis
(creatinine clearance 4-11 ml min-1) and in seven patients with impaired
renal function (creatinine clearance 32-49 ml min-1), during
thiopentone-fentanyl-midazolam-nitrous oxide-oxygen anaesthesia. Mivacurium
chloride was infused at a rate of 15 micrograms kg-1 min-1 for 10 min, 7.5
micrograms kg-1 min-1 for a further 10 min, and then at a rate adjusted to
maintain T1/T0 at 5%. The minimum duration of infusion was 60 min (range
60-235 min). The plasma concentration of the three isomers was measured at
regular intervals throughout the infusion, and for up to 300 min after the
infusion was stopped. Compartmental analysis of the resulting isomer
profiles was undertaken: one- and two-compartment models were fitted to
derive clearance, volume of distribution and terminal elimination
half-life. Clearance of the cis-cis isomer was reduced significantly in the
renal failure (median 2.4 (range 2.1-2.6) ml kg-1 min-1) and intermediate
renal function groups (2.1 (2.0-2.9) ml kg-1 min-1), compared with healthy
patients (3.8 (2.6-4.9) ml kg-1 min-1) (P < 0.01 in each case). There
was no significant difference, within the sample size studied, between the
clearance of the cis-trans isomer, in health (106 (26-147) ml kg-1 min-1),
in renal failure (80 (22-135) ml kg-1 min-1) or with impaired renal
function (87 (58-101) ml kg-1 min-1); or of the trans-trans isomer (57
(18-79) ml kg-1 min-1), (47 (16-88) ml kg-1 min-1) and (44 (40-55) ml kg-1
min-1), respectively). Clearance of each isomer correlated significantly
with plasma cholinesterase activity (cis-trans, r = 0.55, P < 0.01;
trans-trans, r = 0.62, P < 0.01), although this could be demonstrated
only in healthy patients for the cis-cis isomer (r = 0.67, P < 0.05).
There was no significant difference in the terminal half-lives of any
isomer between the groups: cis-cis, healthy (68 (41-204) min), renal
failure (80 (55-153) min), impaired renal function (101 (66-157) min);
cis-trans, healthy (2.0 (1.3-4.4) min), renal failure (4.3 (2.3-7.8) min),
impaired renal function (3.5 (1.4-10.4) min; trans-trans, healthy (2.3
(1.6-8.1) min), renal failure (4.2 (2.4-7.3) min), impaired renal function
(13.4 (2.1-50) min). Volume of distribution was similar for each isomer in
all three groups. The median infusion rate required to maintain T1/T0 at 5%
was significantly increased in the impaired renal function group, at 10.0
micrograms kg-1 min-1, compared with both healthy patients (5.9 micrograms
kg-1 min-1) and renal failure patients (5.0 micrograms kg-1 min-1) (P <
0.05 in each case).
CLINICAL INVESTIGATIONS
Pharmacokinetics and pharmacodynamics of the three isomers of mivacurium in health, in end-stage renal failure and in patients with impaired renal function
University Department of Anaesthesia, Royal Liverpool University Hospital, PO Box 147, Prescot Street, Liverpool L69 3BX
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