Effect of edrophonium and neostigmine on the pharmacokinetics and neuromuscular effects of mivacurium.
BACKGROUND
Previous studies demonstrated that both edrophonium and neostigmine affect mivacurium's pharmacokinetics, thereby potentially affecting its recovery profile. However, those studies were not clinically relevant because mivacurium was still infused after the antagonists were given. In the present study, the authors gave antagonists (or placebo) after discontinuing a mivacurium infusion, thereby obtaining data that are more clinically relevant.


METHODS
In 18 patients, mivacurium was infused at 10 microg kg(-1) x min(-1) for 40 min, the infusion was discontinued for 15 min and then restarted at the same rate for another 40 min. Patients were randomized to receive 500 microg/kg edrophonium, 50 microg/kg neostigmine, or saline at discontinuation of the second infusion; all subjects received 1 mg atropine. Plasma was sampled during the final 10 min of each infusion to determine steady state mivacurium concentrations and for 15 min after each infusion. Twitch tension was recorded. Mivacurium concentrations after each of the two infusions were compared.


RESULTS
After discontinuation of the second infusion, mivacurium concentrations were larger than those after the first infusion at 2 min with edrophonium and at 2, 4, and 7 min with neostigmine. With both neostigmine and edrophonium, twitch tension recovered after infusion #2 more rapidly than after infusion #1; however, the magnitude of this effect was small


CONCLUSIONS
Edrophonium transiently slows the rate at which mivacurium concentrations decrease; this is consistent with our previous findings. Neostigmine has a similar, although longer, effect. Despite altering mivacurium's elimination characteristics, both drugs facilitate neuromuscular recovery, although their benefit is small.
Szenohradszky
J
J
Department of Anesthesia, University of Southern California, Los Angeles, USA.
Fogarty
D
D
Kirkegaard-Nielsen
H
H
Brown
R
R
Sharma
M L
ML
Fisher
D M
DM
D000328:Adult; D000368:Aged; D000375:Aging / Q000502:physiology; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D004347:Drug Interactions; D004491:Edrophonium / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007546:Isoquinolines / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D000077590:Mivacurium; D009119:Muscle Contraction / Q000187:drug effects; D018482:Muscle, Skeletal / Q000187:drug effects / Q000502:physiology; D009388:Neostigmine / Q000494:pharmacology*; D003473:Neuromuscular Nondepolarizing Agents / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology*; D013237:Stereoisomerism; D014459:Ulnar Nerve / Q000187:drug effects / Q000502:physiology
D002800:Cholinesterase Inhibitors; D007546:Isoquinolines; D003473:Neuromuscular Nondepolarizing Agents; D009388:Neostigmine; D004491:Edrophonium; D000077590:Mivacurium