Pharmacokinetics of rapacuronium in infants and children with intravenous and intramuscular administration.
BACKGROUND
A nondepolarizing muscle relaxant with an onset and offset profile similar to succinylcholine is desirable for pediatric anesthesia. The onset and offset of rapacuronium are rapid in children. In the current study, the authors determined its pharmacokinetic characteristics in children. In addition to administering rapacuronium by the usual intravenous route, the authors also gave rapacuronium intramuscularly to determine uptake characteristics and bioavailability.


METHODS
Forty unpremedicated patients aged 2 months to 3 yr were anesthetized with halothane, 0.82-1.0% end-tidal concentration. When anesthetic conditions 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 obtained 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 plasma concentration with intramuscular administration.


RESULTS
Plasma clearance was 4.77 ml x kg(-1) x min(-1) + 8.48 ml/min. Intramuscular bioavailability averaged 56%. Absorption from the intramuscular depot had two rate constants: 0.0491 min(-1) (72.4% of absorbed drug) and 0.0110 min(-1) (27.6% of the absorbed drug). Simulation indicated that plasma concentration peaks 4.0 and 5.0 min after intramuscular rapacuronium in infants and children, respectively, and that, at 30 min, less than 25% of the administered dose remains to be absorbed from the intramuscular depot.


CONCLUSIONS
In infants and children, rapacuronium's clearance and steady state distribution volume are less than in adults. After intramuscular administration, bioavailability is 56%, and plasma rapacuronium concentrations peak within 4 or 5 min.
Reynolds
L M
LM
Department of Anesthesia and Perioperative Care, University of California, San Francisco 94143-0648, USA.
Infosino
A
A
Brown
R
R
Hsu
J
J
Fisher
D M
DM
D000465:Algorithms; D000758:Anesthesia; D001682:Biological Availability; D002675:Child, Preschool; D005260:Female; D006207:Half-Life; D006801:Humans; D007223:Infant; D007273:Injections, Intramuscular; D007275:Injections, Intravenous; D008297:Male; D008954:Models, Biological; D003473:Neuromuscular Nondepolarizing Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D014673:Vecuronium Bromide / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics
D003473:Neuromuscular Nondepolarizing Agents; D014673:Vecuronium Bromide; C082938:rapacuronium