Pharmacokinetics of mivacurium in normal patients and in those with hepatic or renal failure.
We have determined the pharmacokinetics and duration of action of a bolus dose of mivacurium (0.15 mg kg-1) during isoflurane and nitrous oxide anaesthesia in nine patients with normal renal and liver function, nine patients undergoing cadaveric kidney transplantation and nine patients undergoing cadaveric liver transplantation. Total plasma concentrations of mivacurium were measured for 2.5 h after administration using a high-pressure liquid chromatographic assay. Plasma concentration vs time data for what were presumed to be the two active mivacurium isomers were analysed by a non-compartmental method based on statistical moments. Neuromuscular block was assessed by measuring the electromyographic evoked response of the adductor pollicis muscle to train-of-four stimulation of the ulnar nerve. The mean time to recovery of 25% neuromuscular transmission, T25, was greater in the patients with liver failure (57.2 min) than in control patients (18.7 min). The volume of distribution at steady rate (Vdss) was comparable in the three groups. Patients with impaired liver function had significantly longer mean residence time and smaller plasma clearance than did patients with renal failure or control patients. There were significant negative correlations between plasma cholinesterase activity and both T25 (r = 0.79) and mean residence time (r = 0.62).
Cook
D R
DR
Department of Anesthesiology, Presbyterian University Hospital, Pittsburgh, Pennsylvania.
Freeman
J A
JA
Lai
A A
AA
Kang
Y
Y
Stiller
R L
RL
Aggarwal
S
S
Harrelson
J C
JC
Welch
R M
RM
Samara
B
B
D000328:Adult; D002802:Cholinesterases / Q000097:blood; D005260:Female; D006801:Humans; D007536:Isomerism; D007546:Isoquinolines / Q000493:pharmacokinetics* / Q000494:pharmacology; D007668:Kidney / Q000378:metabolism; D007676:Kidney Failure, Chronic / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D017093:Liver Failure / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D000077590:Mivacurium; D009469:Neuromuscular Junction / Q000502:physiology; D003473:Neuromuscular Nondepolarizing Agents / Q000493:pharmacokinetics*; D009435:Synaptic Transmission / Q000187:drug effects; D013997:Time Factors
D007546:Isoquinolines; D003473:Neuromuscular Nondepolarizing Agents; D000077590:Mivacurium; D002802:Cholinesterases