PHARMACOKINETICS AND PHARMACOKINETIC-DYNAMIC MODELING OF ROCURONIUM IN INFANTS AND CHILDREN

We have determined the pharmacokinetics and pharmacokinetic-pharmacody namic relationship of rocuronium in infants and children. We studied i nfants (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. anaesthesia with an arterial cannula in situ and the EMG of the adductor pollicis muscle was monitored. Rocuronium 0.06 (infants) and 0.09 (children) m g kg(-1) min(-1) was given i.v. over +/- 5 min until 85% neuromuscular block was obtained. Arterial blood samples were obtained over 240 min . Plasma concentrations were measured by HPLC. Pharmacokinetic-dynamic variables were calculated using the Sheiner model and the Hill equati on. Statistical analysis was performed using the Mann-Whitney U test ( P < 0.05). The mean administered dose was 0.32 (SD 0.08) mg kg(-1) and 0.4 (0.1) mg kg(-1) for infants and children, respectively. infants d iffered from children in plasma clearance (4.2 (0.4) vs 6.7 (1.1) ml m in(-1) kg(-1)), distribution volume at steady state (231 (32) vs 165 ( 44) ml kg(-1)), mean residence time (56 (10) vs 26 (9) min), concentra tion in the effect compartment at 50% block (1.2 (0.4) vs 1.7 (0.4) mg litre(-1)) and the slope of the concentration-effect relationship (5. 7 (1.3) vs 3.9 (0.5)). Calculated mean ED90 values were 0.26 and (0.34 mg kg(-1) for infants and children, respectively. The time course of neuromuscular block after equipotent doses did not differ.