The pharmacodynamics and pharmacokinetics of mivacurium in children.
BACKGROUND
In children, onset time and duration of action of mivacurium are shorter than in adults. Some suggest that this is due to differences in plasma cholinesterase (pChe), whereas others indicate that there is no difference. The purpose of this study was to evaluate the pharmacodynamics and pharmacokinetics of mivacurium in phenotypically normal children aged 3-6 and 10-14 years old, respectively.


METHODS
Ten children aged 3-6 years and 10 children aged 10-14 years were studied during halothane anaesthesia. Before induction of anaesthesia, a blood sample was drawn to measure the pChe activity and phenotype. The neuromuscular block was monitored at the thumb using train-of-four (TOF) nerve stimulation every 12 s and mechanomyography. The times to different levels of neuromuscular recovery following mivacurium 0.2 mg/kg were recorded. The concentrations in venous blood of the three isomers and the metabolites of mivacurium were measured.


RESULTS
No statistically significant difference was found in pChe activity or in the pharmacodynamics of mivacurium. The onset time was 1.4 min (0.8-1.9) median (range) and 1.3 min (1.1-1.9) and the time to first response to TOF nerve stimulation was 9.6 min (6.5-12.6) and 10.5 min (7.0-14.0) in young and older children, respectively. The pharmacokinetic data were too sparse to allow analysis of the two age groups separately (8 and 8 patients), hence the data were pooled. The median clearances of the cis-cis, the cis-trans, and the trans-trans isomer were 5.5, 51.0 and 30.5 ml/kg/min, respectively.


CONCLUSIONS
Our data indicate that there are no major differences in pharmacodynamics or pharmacokinetics of mivacurium between young (3-6 years) and older (10-14 years) children.
ØStergaard
D
D
Danish Cholinesterase Research Unit, Department of Anaesthesia and Intensive Care, Copenhagen University Hospital, Rigshospitalet, Denmark. dooe@herlevhosp.kbhamt.dk
Gätke
M R
MR
Berg
H
H
Rasmussen
S N
SN
Viby-Mogensen
J
J
D000293:Adolescent; D000465:Algorithms; D000769:Anesthesia, Inhalation; D019540:Area Under Curve; D002648:Child; D002675:Child, Preschool; D002802:Cholinesterases / Q000097:blood; D004558:Electric Stimulation; D005260:Female; D006207:Half-Life; D006801:Humans; D007546:Isoquinolines / Q000493:pharmacokinetics* / Q000494:pharmacology*; D008297:Male; D000077590:Mivacurium; D016343:Monitoring, Intraoperative; D009213:Myography; D003473:Neuromuscular Nondepolarizing Agents / Q000493:pharmacokinetics* / Q000494:pharmacology*; D013237:Stereoisomerism
D007546:Isoquinolines; D003473:Neuromuscular Nondepolarizing Agents; D000077590:Mivacurium; D002802:Cholinesterases