Pharmacokinetics and pharmacokinetic-dynamic modelling of rocuronium in infants and children

We have determined the pharmacokinetics and pharmacokinetic-pharmacodynamic relationship of rocuronium in infants and children. Westudied infants (n = 5, 0.1-0.8 yr) and children (n = 5, 2.3-8 yr), ASA II,in the ICU while undergoing artificial ventilation under i.v. anaesthesiawith an arterial cannula in situ and the EMG of the adductor pollicismuscle was monitored. Rocuronium 0.06 (infants) and 0.09 (children) mg kg-1min-1 was given i.v. over +/- 5 min until 85% neuromuscular block wasobtained. Arterial blood samples were obtained over 240 min. Plasmaconcentrations were measured by HPLC. Pharmacokinetic-dynamic variableswere calculated using the Sheiner model and the Hill equation. Statisticalanalysis was performed using the Mann-Whitney U test (P < 0.05). Themean administered dose was 0.32 (SD 0.08) mg kg-1 and 0.4 (0.1) mg kg-1 forinfants and children, respectively. Infants differed from children inplasma clearance (4.2 (0.4) vs 6.7 (1.1) ml min-1 kg-1), distributionvolume at steady state (231 (32) vs 165 (44) ml kg-1), mean residence time(56 (10) vs 26 (9) min), concentration in the effect compartment at 50%block (1.2 (0.4) vs 1.7 (0.4) mg litre-1) and the slope of theconcentration-effect relationship (5.7 (1.3) vs 3.9 (0.5)). Calculated meanED90 values were 0.26 and 0.34 mg kg-1 for infants and children,respectively. The time course of neuromuscular block after equipotent dosesdid not differ.