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Pharmacokinetics of rapacuronium in infants and children with intravenous and intramuscular administration
L M Reynolds1, A Infosino, R Brown
1Department of Anesthesia and Perioperative Care, University of California, San Francisco 94143-0648, USA.
Insights
Rapacuronium offers rapid onset and offset in pediatric anesthesia. Intramuscular administration shows 56% bioavailability, with peak plasma concentrations reached within 4-5 minutes in infants and children.
Area of Science:
- Pharmacology
- Anesthesiology
- Pediatric Medicine
Background:
- Nondepolarizing muscle relaxants with succinylcholine-like profiles are needed for pediatric anesthesia.
- Rapacuronium exhibits rapid onset and offset in pediatric patients.
- This study investigated rapacuronium's pharmacokinetic properties in children.
Purpose of the Study:
- To determine the pharmacokinetic characteristics of rapacuronium in pediatric patients.
- To evaluate rapacuronium's uptake and bioavailability following intramuscular administration.
- To compare intravenous and intramuscular administration routes.
Main Methods:
- Forty pediatric patients (2 months to 3 years) received halothane anesthesia.
- Rapacuronium was administered intravenously (2-3 mg/kg) or intramuscularly (2.8-4.8 mg/kg).
- Population pharmacokinetic analysis was used to assess bioavailability and absorption kinetics.
Main Results:
- Intramuscular rapacuronium demonstrated an average bioavailability of 56%.
- Absorption from intramuscular sites followed biphasic kinetics with rate constants of 0.0491 min⁻¹ and 0.0110 min⁻¹.
- Peak plasma concentrations were observed at 4.0 minutes in infants and 5.0 minutes in children after intramuscular injection.
Conclusions:
- Rapacuronium clearance and steady-state volume of distribution are lower in pediatric patients compared to adults.
- Intramuscular administration of rapacuronium yields 56% bioavailability.
- Plasma concentrations peak rapidly within 4-5 minutes post-intramuscular administration in pediatric populations.
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.