The pharmacokinetics and steady state pharmacodynamics of mivacurium in children

Background: The authors previously show-ed 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 (Cltrans-trans) and cis-trans (Clcis-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, C-90. The effect of age on cholinesterase activity, the infusion rate depressing twitch tension by 90% (IR90), C-90, Cltrans-trans, and Clcis-trans was determined using Linear regression. Results: Cholinesterase activity, 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 larger in lounger patients, consistent with the larger mivacurium infusion requirement in children than hi adults reported previously.