THE PHARMACOKINETICS AND STEADY-STATE PHARMACODYNAMICS OF MIVACURIUM IN CHILDREN

Background: The authors previously show-ed that children require Large r infusion rates of mivacurium than adults to maintain target twitch d epression. Here, they determined whether there are differences between children and adults in mivacurium's pharmacokinetic and pharmacodynam ic properties. Methods: Twenty-seven patients aged 1-58 yr were anesth etized 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 i n infusion rate for 15 min, plasma was sampled to determine concentrat ions of mivacurium's stereoisomers. Clearance of the trans-trans (Cltr ans-trans) and cis-trans (Clcis-trans) isomers was determined as the m ivacurium infusion rate (adjusted for isomer composition) divided by t he concentration of that isomer. Using the Hill equation, assuming equ ipotency of the trans-trans and cis-trans isomers, and ignoring the co ntribution of the nonpotent cis-cis isomer, the authors estimated the steady state plasma concentration yielding 90% twitch depression, C-90 . The effect of age on cholinesterase activity, the infusion rate depr essing twitch tension by 90% (IR90), C-90, Cltrans-trans, and Clcis-tr ans was determined using Linear regression. Results: Cholinesterase ac tivity, IR90, and C-90 did not vary with age. Both Cltrans-trans (r(2) = 0.19, P = 0.01) and Clcis-trans, (r(2) = 0.19, P = 0.02) decreased with age. Conclusion: Clearance of mivacurium's potent isomers is larg er in lounger patients, consistent with the larger mivacurium infusion requirement in children than hi adults reported previously.