The influence of drug-induced low plasma cholinesterase activity on the pharmacokinetics and pharmacodynamics of mivacurium.
BACKGROUND
The short duration of action of mivacurium results from its rapid hydrolysis by plasma cholinesterase. Bambuterol, an oral bronchodilator, has an inhibiting effect on plasma cholinesterase. The purpose of this study was to evaluate the effect of bambuterol-induced low plasma cholinesterase activity on the pharmacokinetics and pharmacodynamics of mivacurium.


METHODS
Fourteen patients received 20 mg bambuterol and 14 patients received placebo orally 2 h before induction of anesthesia. During anesthesia the neuromuscular block was monitored at the thumb using train-of-four nerve stimulation every 12 s and mechanomyography. The times to different levels of neuromuscular recovery after 0.2 mg/kg mivacurium were measured. The concentrations in venous blood of the three isomers and the metabolites of mivacurium were measured using high-performance liquid chromatography.


RESULTS
Plasma cholinesterase activity was inhibited a median of 90% (range, 67-97%) after bambuterol. The time to first response to train-of-four nerve stimulation was 15 min (range, 9-21 min) and 59 min (range, 32-179 min) in patients receiving placebo and bambuterol, respectively. The estimated clearances of the isomers were significantly lower and the elimination half-lives of all three isomers significantly prolonged in patients receiving bambuterol. No difference was seen in elimination half-lives of the metabolites. The elimination rate constant from the effect compartment and the potency of mivacurium was not affected by bambuterol.


CONCLUSIONS
A 90% inhibition of plasma cholinesterase activity significantly reduced clearance of the isomers of mivacurium. Correspondingly, the duration of action of 0.2 mg/kg mivacurium was prolonged three- to fourfold, compared with patients not administered bambuterol.
Ostergaard
D
D
Department of Anesthesiology, Gentofte University Hospital, Copenhagen, Denmark. dooe@herlevhosp.kbhamt.dk
Rasmussen
S N
SN
Viby-Mogensen
J
J
Pedersen
N A
NA
Boysen
R
R
D000328:Adult; D000368:Aged; D001993:Bronchodilator Agents / Q000494:pharmacology*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D002802:Cholinesterases / Q000097:blood*; D004311:Double-Blind Method; D004336:Drug Antagonism; D005260:Female; D006207:Half-Life; D006801:Humans; D007546:Isoquinolines / Q000493:pharmacokinetics* / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D000077590:Mivacurium; D003473:Neuromuscular Nondepolarizing Agents / Q000493:pharmacokinetics* / Q000494:pharmacology; D013237:Stereoisomerism; D013726:Terbutaline / Q000031:analogs & derivatives* / Q000494:pharmacology
D001993:Bronchodilator Agents; D002800:Cholinesterase Inhibitors; D007546:Isoquinolines; D003473:Neuromuscular Nondepolarizing Agents; D000077590:Mivacurium; D002802:Cholinesterases; D013726:Terbutaline; C047766:bambuterol