The pharmacokinetics and steady state pharmacodynamics of mivacurium in children.
BACKGROUND
The authors previously showed that children require larger infusion rates of mivacurium than adults to maintain target twitch depression. Here, they determined whether there are differences between children and adults in mivacurium's pharmacokinetic and pharmacodynamic properties.


METHODS
Twenty-seven patients aged 1-58 yr were anesthetized with nitrous oxide and isoflurane. Cholinesterase activity and adductor pollicis twitch tension in response to train-of-four stimuli were measured. Mivacurium was infused, targeting 90% twitch depression. When twitch was stably depressed 85%-95% for 10 min with no change in infusion rate for 15 min, plasma was sampled to determine concentrations of mivacurium's stereoisomers. Clearance of the trans-trans (Cl(trans-trans)) and cis-trans (Cl(cis-trans)) isomers was determined as the mivacurium infusion rate (adjusted for isomer composition) divided by the concentration of that isomer. Using the Hill equation, assuming equipotency of the trans-trans and cis-trans isomers, and ignoring the contribution of the nonpotent cis-cis isomer, the authors estimated the steady state plasma concentration yielding 90% twitch depression, C90. The effect of age on cholinesterase activity, the infusion rate depressing twitch tension by 90% (IR90), C90, Cl(trans-trans), and Cl(cis-trans) was determined using linear regression.


RESULTS
Cholinesterase activity, IR90, and C90 did not vary with age. Both Cl(trans-trans) (r2 = 0.19, P = 0.01) and Cl(cis-trans) (r2 = 0.19, P = 0.02) decreased with age.


CONCLUSIONS
Clearance of mivacurium's potent isomers is larger in younger patients, consistent with the larger mivacurium infusion requirement in children than in adults reported previously.
Markakis
D A
DA
Department of Anesthesia, University of California, San Francisco, 94143-0648, USA.
Lau
M
M
Brown
R
R
Luks
A M
AM
Sharma
M L
ML
Fisher
D M
DM
D000293:Adolescent; D000328:Adult; D000375:Aging / Q000378:metabolism*; D000769:Anesthesia, Inhalation; D018685:Anesthetics, Inhalation; D002648:Child; D002675:Child, Preschool; D002802:Cholinesterases / Q000097:blood; D006801:Humans; D007223:Infant; D007262:Infusions, Intravenous; D007530:Isoflurane; D007546:Isoquinolines / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D000077590:Mivacurium; D003473:Neuromuscular Nondepolarizing Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D009609:Nitrous Oxide; D013237:Stereoisomerism
D018685:Anesthetics, Inhalation; D007546:Isoquinolines; D003473:Neuromuscular Nondepolarizing Agents; D000077590:Mivacurium; D007530:Isoflurane; D002802:Cholinesterases; D009609:Nitrous Oxide