Caudal ropivacaine in infants - Population pharmacokinetics and plasma concentrations

Background Ropivacaine is a new long-acting amino-amide local anesthetic. H owever, there are no data on its use in infants. In the current study, the authors investigated the pharmacokinetics of caudal ropivacaine in 30 infan ts 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% ropivaca ine (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 mo deling was performed to yield estimates of clearance, volume of distributio n, and absorption rate constant. An analysis of covariates on the kinetic p arameters also was made. Results: Median maximum free ropivacaine concentration was significantly hi gher in group 1 (99 mug/l) than in group 2 (38 mug/l) (P = 0.0002), as was the median free fraction of ropivacaine (10% vs. 5 %; P = 0.01), Pharmacoki netic variables of the total population were best described by a one-compar tment 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. A ge and percentage of free ropivacaine were significant covariates for clear ance. Posterior Bayesian estimates of clearance were significantly higher ( 38%) in older children. Conclusion: Total and free plasma ropivacaine concentrations after caudal r opivacaine (0.2%, 2 mg/kg) in infants were within the range of concentratio ns previously reported in adults and older children. Age and percentage of free ropivacaine were significant covariates of clearance.