PHARMACOKINETICS AND PHARMACODYNAMICS OF THE 3 ISOMERS OF MIVACURIUM IN HEALTH, IN END-STAGE RENAL-FAILURE AND IN PATIENTS WITH IMPAIRED RENAL-FUNCTION
Ag. Headrapson et al., PHARMACOKINETICS AND PHARMACODYNAMICS OF THE 3 ISOMERS OF MIVACURIUM IN HEALTH, IN END-STAGE RENAL-FAILURE AND IN PATIENTS WITH IMPAIRED RENAL-FUNCTION, British Journal of Anaesthesia, 75(1), 1995, pp. 31-36
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 thiopenton-fentanyl-midazolam-nitrous oxide-oxygen anaesthesia.
Mivacurium chloride was infused at a rate of 15 mu g kg(-1) min(-1) f
or 10 min, 7.5 mu g 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 infusi
on was 60 min (range 60-235 min). The plasma concentration of the thre
e isomers was measured at regular intervals throughout the infusion, a
nd for up to 300 min after the infusion was stopped. Compartmental ana
lysis of the resulting isomer profiles was undertaken: one- and two-co
mpartment models were fitted to derive clearance, volume of distributi
on 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 signific
ant difference, within the sample size studied, between the clearance
of the cis-trans isomer, in health (106 (26-147) ml kg(-1) min(-1)), i
n 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 isome
r (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-tra
ns, r = 0.55, P < 0.01; trans-trans, r = 0.62, P < 0.01), although thi
s could be demonstrated only in healthy patients for the cis-cis isome
r (r = 0.67, P < 0.05). There was no significant difference in the ter
minal half-lives of any isomer between the groups: cis-cis, healthy (6
8 (41-204) min), renal failure (80 (55-153) min), impaired renal funct
ion (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) m
in; 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 dist
ribution was similar for each isomer in all three groups. The median i
nfusion rate required to maintain T1/TO at 5% was significantly increa
sed in the impaired renal function group, at 10.0 mu g kg(-1) min(-1),
compared with both healthy patients (5.9 mu g kg(-1) min(-1)) and ren
al failure patients (5.0 mu g kg(-1) min(-1)) (P < 0.05 in each case).