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Caudal ropivacaine in infants: population pharmacokinetics and plasma concentrations
T G Hansen1, K F Ilett, C Reid
1Department of Paediatric Anaesthesia, Princess Margaret Hospital for Children, Western Australia. tomghansen@dadlnet.dk
Insights
Pharmacokinetics of caudal ropivacaine in infants showed that concentrations were similar to adults. Clearance was influenced by age, with older infants exhibiting higher clearance rates for this local anesthetic.
Area of Science:
- Pediatric Anesthesiology
- Pharmacokinetics
- Local Anesthetics
Background:
- Ropivacaine, a long-acting amino-amide local anesthetic, lacks pharmacokinetic data in infants.
- This study addresses the knowledge gap regarding caudal ropivacaine use in this population.
Purpose of the Study:
- To investigate the pharmacokinetics of caudal ropivacaine in infants younger than 12 months.
- To determine the influence of age on ropivacaine pharmacokinetics.
Main Methods:
- 30 infants (<12 months) were divided into two age groups (0-3 and 3-12 months).
- Caudal ropivacaine (0.2%, 2 mg/kg) was administered with a standardized anesthetic technique.
- Serial blood samples were analyzed for total and free ropivacaine using HPLC, with population pharmacokinetic modeling.
Main Results:
- Higher median maximum free ropivacaine concentrations and free fractions were observed in younger infants (0-3 months) compared to older infants (3-12 months).
- A one-compartment model best described population pharmacokinetics.
- Mean clearance was 0.31 L/h/kg, volume of distribution was 2.12 L/kg, and absorption rate constant was 1.61 h⁻¹.
- Age and free ropivacaine percentage were significant covariates for clearance, with older children showing 38% higher clearance.
Conclusions:
- Plasma concentrations of ropivacaine in infants were comparable to those in adults and older children.
- Age and the percentage of free ropivacaine are significant determinants of clearance in infants.
Background:
Ropivacaine is a new long-acting amino-amide local anesthetic. However, there are no data on its use in infants. In the current study, the authors investigated the pharmacokinetics of caudal ropivacaine in 30 infants younger than 12 months.
Methods:
Two groups of infants (group 1 [n = 15], aged 0-3 months; group 2 [n = 15], aged 3-12 months) were given a caudal bolus dose of 0.2% ropivacaine (2 mg/kg) and a standardized general anesthetic technique. Serial blood samples taken for up to 12 h were analyzed for total and free ropivacaine using high-performance liquid chromatography. Population pharmacokinetic modeling was performed to yield estimates of clearance, volume of distribution, and absorption rate constant. An analysis of covariates on the kinetic parameters also was made.
Results:
Median maximum free ropivacaine concentration was significantly higher in group 1 (99 micog/l) than in group 2 (38 microg/l) (P = 0.0002), as was the median free fraction of ropivacaine (10% vs. 5%; P = 0.01). Pharmacokinetic variables of the total population were best described by a one-compartment model with first-order absorption. Mean clearance was 0.31 l.h(-1).kg(-1) (coefficient of variation [CV], 51%), volume of distribution was 2.12 l/kg (CV, 34%), and absorption rate constant was 1.61 h(-1) (CV, 46%). Mean absorption and elimination half-lives were 0.43 and 5.1 h, respectively. Age and percentage of free ropivacaine were significant covariates for clearance. Posterior Bayesian estimates of clearance were significantly higher (38%) in older children.
Conclusion:
Total and free plasma ropivacaine concentrations after caudal ropivacaine (0.2%, 2 mg/kg) in infants were within the range of concentrations previously reported in adults and older children. Age and percentage of free ropivacaine were significant covariates of clearance.