Dosing of Continuous Fentanyl Infusions in Obese Children: A Population Pharmacokinetic Analysis.

Published online

Journal Article

Differences in fentanyl pharmacokinetics (PK) between obese and nonobese adults have previously been reported; however, the impact of childhood obesity on fentanyl PK is relatively unknown. We developed a population pharmacokinetic (PopPK) model using opportunistically collected samples from a cohort of predominately obese children receiving fentanyl per the standard of care. Using a probability-based approach, we evaluated the ability of different continuous infusion strategies to provide steady-state concentrations (Css ) within an analgesic concentration range (1-3 ng/mL). Fifty-three samples from 32 children were used for PopPK model development. Median (range) age and body weight of study participants were 13 years (2-19 years) and 52 kg (16-164 kg), respectively. The majority of children (94%) were obese. A 2-compartment model allometrically scaled by total body weight provided an appropriate fit to the data. Estimated typical clearance was 32.5 L/h (scaled to 70 kg). A fixed dose rate infusion of 1 µg/kg/h was associated with probabilities between 49% and 58% for achieving Css within target; however, the risk of achieving Css > 3 ng/mL increased with increasing body weight (15% at 16 kg vs 43% at 164 kg). A proposed model-based infusion strategy maintained consistent probabilities across the examined weight range for achieving Css within (58%) and above (20%) target. Use of an allometric relationship between weight and clearance was appropriate for describing the PK of intravenous fentanyl in our cohort of predominately obese children. Our proposed model-derived continuous infusion strategy maximized the probability of achieving target Css in children of varying weights.

Full Text

Duke Authors

Cited Authors

  • Maharaj, AR; Wu, H; Zimmerman, KO; Speicher, DG; Sullivan, JE; Watt, K; Al-Uzri, A; Payne, EH; Erinjeri, J; Lin, S; Harper, B; Melloni, C; Hornik, CP; Best Pharmaceuticals for Children Act - Pediatric Trials Network Steering Committee,

Published Date

  • December 8, 2019

Published In

PubMed ID

  • 31814149

Pubmed Central ID

  • 31814149

Electronic International Standard Serial Number (EISSN)

  • 1552-4604

Digital Object Identifier (DOI)

  • 10.1002/jcph.1562

Language

  • eng

Conference Location

  • England