• Rzasa LynnRachael SRSFrom the Department of Anesthesiology, University of Colorado School of Medicine, Aurora, Colorado., Thomas K Henthorn, Jeannie Zuk, Gregory B Hammer, David R Drover, Richard J Levy, Lynne G Maxwell, Senthilkumar Sadhasivam, Santhanam Suresh, and Jeffrey L Galinkin.
• From the Department of Anesthesiology, University of Colorado School of Medicine, Aurora, Colorado.
• Anesth. Analg. 2024 Feb 1; 138 (2): 447455447-455.

BackgroundFentanyl is widely used for analgesia and sedation in neonates, but pharmacokinetic (PK) analysis in this population has been limited by the relatively large sample volumes required for plasma-based assays.MethodsIn this multicenter observational study of fentanyl kinetics in neonates up to 42 weeks of postmenstrual age (PMA) who received fentanyl boluses and continuous infusions, dried blood spots were used for small-volume sampling. A population PK analysis was used to describe fentanyl disposition in term and preterm neonates. Covariates for the model parameters, including body weight, PMA, birth status (preterm or term), and presence of congenital cardiac disease, were assessed in a stepwise manner.ResultsClearance was estimated to be greater than adult clearance of fentanyl and varied with weight. Covariate selection did not yield a significant relationship for age as a continuous or dichotomous variable (term or preterm, the latter defined as birth with PMA of <37 weeks) and clearance.ConclusionsA supra-allometric effect on clearance was determined during covariate analyses (exponential scaling factor for body weight >0.75), as has been described in population PK models that account for maturation of intrinsic clearance (here, predominantly hepatic microsomal activity) in addition to scaling for weight, both of which impact clearance in this age group.Copyright © 2023 International Anesthesia Research Society.

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