Pharmacokinetics and pharmacodynamics of mivacurium in patients phenotypically homozygous for the atypical plasma cholinesterase variant: effect of injection of human cholinesterase.
BACKGROUND
In patients homozygous for atypical plasma cholinesterase, mivacurium causes a long-lasting neuromuscular block, but injection of human cholinesterase has been proven effective in antagonizing the block. The purpose of this study was to evaluate the pharmacodynamics and pharmacokinetics of mivacurium in such patients, as well as the effect of cholinesterase injected early or late after mivacurium.


METHODS
Eleven patients phenotypically homozygous for the atypical variant received 0.075 mg/kg (1 patient) or 0.15 mg/kg (10 patients) mivacurium. The neuromuscular block was monitored using train-of-four nerve stimulation and mechanomyography. Cholinesterase, 2.8-10.0 mg/kg, was administered approximately 30 or 120 min after mivacurium. The times to different levels of neuromuscular recovery and the venous concentrations of the isomers of mivacurium were measured.


RESULTS
Injection of cholinesterase increased plasma cholinesterase activity to normal and the clearances of the active isomers and the elimination rate constants by a factor of 10-15. The first response was seen in 13.5 min (3.7-44.2 min). Time to a train-of-four ratio of 0.8 ranged from 30 to 60 min (n = 6). Neostigmine injected after cholinesterase shortened recovery further, and a train-of-four ratio of 0.8 was reached in 10-30 min.


CONCLUSIONS
As expected, the duration of action of mivacurium is markedly prolonged in homozygous atypical patients. Injection of cholinesterase significantly increases the metabolism of mivacurium, leading to a shorter duration of action. Injection of neostigmine after the administration of cholinesterase speeds up recovery.
Østergaard
Doris
D
Department of Anesthesia, Herlev University Hospital, Herlev Ringvej, DK-2730 Herlev, Denmark. dooe@herlevhosp.kbhamt.dk
Viby-Mogensen
Jørgen
J
Rasmussen
Søren N
SN
Gätke
Mona R
MR
Varin
France
F
D000293:Adolescent; D000328:Adult; D002802:Cholinesterases / Q000008:administration & dosage* / Q000097:blood / Q000235:genetics*; D005260:Female; D014644:Genetic Variation / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D007546:Isoquinolines / Q000097:blood* / Q000493:pharmacokinetics / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D000077590:Mivacurium; D010641:Phenotype
D007546:Isoquinolines; D000077590:Mivacurium; D002802:Cholinesterases