Pharmacokinetics of rapacuronium in infants and children with intravenous and intramuscular administration

Background: A nondepolarizing muscle relaxant with an onset and offset prof ile similar to succinylcholine is desirable for pediatric anesthesia. The o nset and offset of rapacuronium are rapid in children. In the current study , the authors determined its pharmacokinetic characteristics in children. I n addition to administering rapacuronium by the usual intravenous route, th e authors also gave rapacuronium intramuscularly to determine uptake charac teristics and bioavailability. Methods: Forty unpremedicated patients aged 2 months to 3 yr were anestheti zed with halothane, 0.82-1.0% end-tidal concentration. When anesthetic cond itions were stable, rapacuronium was injected either into a peripheral vein (2 mg/kg for infants, 3 mg/kg for children) or a deltoid muscle (2.8 mg/kg for infants, 4.8 mg/kg for children). Four venous plasma samples were obta ined from each subject 2-240 min after rapacuronium administration. A mixed -effects population pharmacokinetic analysis was applied to these values to determine bioavailability, absorption rate constant, and time to peak plas ma concentration with intramuscular administration. Results: Plasma clearance was 4.77 ml.kg(-1).min(-1) + 8.48 ml/min. Intramu scular bioavailability averaged 56%. Absorption from the intramuscular depo t had two rate constants: 0.0491 min(-1) (72.4% of absorbed drug) and 0.011 0 min(-1) (27.6% of the absorbed drug). Simulation indicated that plasma co ncentration peaks 4.0 and 5.0 min after intramuscular rapa curonium in infa nts and children, respectively, and that, at 30 min, less than 25% of the a dministered dose remains to be absorbed from the intramuscular depot. Conclusions: In infants and children, rapacuronium's clearance and steady s tate distribution volume are less than in adults. After intramuscular admin istration, bioavailability is 56%, and plasma rapacuronium concentrations p eak within 4 or 5 min.