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Wu Y, Völler S, Flint RB, et al. Pre- and Postnatal Maturation are Important for Fentanyl Exposure in Preterm and Term Newborns: A Pooled Population Pharmacokinetic Study. Clin Pharmacokinet. 2021;doi: 10.1007/s40262-021-01076-0.
Wu, Y., Völler, S., Flint, R. B., Simons, S. H. P., Allegaert, K., Fellman, V., & Knibbe, C. A. J. (2021). Pre- and Postnatal Maturation are Important for Fentanyl Exposure in Preterm and Term Newborns: A Pooled Population Pharmacokinetic Study. Clinical pharmacokinetics, . https://doi.org/10.1007/s40262-021-01076-0
Wu, Yunjiao, et al. "Pre- and Postnatal Maturation are Important for Fentanyl Exposure in Preterm and Term Newborns: A Pooled Population Pharmacokinetic Study." Clinical pharmacokinetics vol. (2021). doi: https://doi.org/10.1007/s40262-021-01076-0
Wu Y, Völler S, Flint RB, Simons SHP, Allegaert K, Fellman V, Knibbe CAJ. Pre- and Postnatal Maturation are Important for Fentanyl Exposure in Preterm and Term Newborns: A Pooled Population Pharmacokinetic Study. Clin Pharmacokinet. 2021 Nov 13; doi: 10.1007/s40262-021-01076-0. Epub 2021 Nov 13. PMID: 34773609.
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Clin Pharmacokinet. 2021 Nov 13; doi: 10.1007/s40262-021-01076-0. Epub 2021 Nov 13.

Pre- and Postnatal Maturation are Important for Fentanyl Exposure in Preterm and Term Newborns: A Pooled Population Pharmacokinetic Study.

Clinical pharmacokinetics

Yunjiao Wu, Swantje Völler, Robert B Flint, Sinno H P Simons, Karel Allegaert, Vineta Fellman, Catherijne A J Knibbe

Affiliations

  1. Systems Biomedicine and Pharmacology, Leiden Academic Centre for Drug Research (LACDR), Leiden University, Leiden, the Netherlands.
  2. Pharmacy, Leiden Academic Centre for Drug Research (LACDR), Leiden University, Leiden, the Netherlands.
  3. Department of Pediatrics, Division of Neonatology, Erasmus MC Sophia Children's Hospital, Rotterdam, the Netherlands.
  4. Department of Hospital Pharmacy, Erasmus University Medical Center, Rotterdam, the Netherlands.
  5. Departments of Development and Regeneration and Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium.
  6. Department of Clinical Sciences, Lund, Pediatrics, Lund University, Lund, Sweden.
  7. Folkhälsan Research Center, Helsinki, Finland.
  8. Children's Hospital, University of Helsinki, Helsinki, Finland.
  9. Systems Biomedicine and Pharmacology, Leiden Academic Centre for Drug Research (LACDR), Leiden University, Leiden, the Netherlands. [email protected].
  10. Department of Pediatrics, Division of Neonatology, Erasmus MC Sophia Children's Hospital, Rotterdam, the Netherlands. [email protected].
  11. Department of Clinical Pharmacy, St Antonius Hospital, Nieuwegein, the Netherlands. [email protected].

PMID: 34773609 DOI: 10.1007/s40262-021-01076-0

Abstract

BACKGROUND AND OBJECTIVE: Fentanyl is an opioid commonly used to prevent and treat severe pain in neonates; however, its use is off label and mostly based on bodyweight. Given the limited pharmacokinetic information across the entire neonatal age range, we characterized the pharmacokinetics of fentanyl across preterm and term neonates to individualize dosing.

METHODS: We pooled data from two previous studies on 164 newborns with a median gestational age of 29.0 weeks (range 23.9-42.3), birthweight of 1055 g (range 390-4245), and postnatal age (PNA) of 1 day (range 0-68). In total, 673 plasma samples upon bolus dosing (69 patients; median dose 2.1 μg/kg, median 2 boluses per patient) or continuous infusions (95 patients; median dose 1.1 μg/kg/h for 30 h) with and without boluses were used for population pharmacokinetic modeling in NONMEM

RESULTS: Clearance in neonates with birthweight of 2000 and 3000 g was 2.8- and 5.0-fold the clearance in a neonate with birthweight of 1000 g, respectively. Fentanyl clearance at PNA of 7, 14, and 21 days was 2.7-fold, 3.8-fold, and 4.6-fold the clearance at 1 day, respectively. Bodyweight-based dosing resulted in large differences in fentanyl concentrations. Depending on PNA and birthweight, fentanyl concentrations increased slowly after the start of therapy for both intermittent boluses and continuous infusion and reached a maximum concentration at 12-48 h.

CONCLUSIONS: As both prenatal and postnatal maturation are important for fentanyl exposure, we propose a birthweight- and PNA-based dosage regimen. To provide rapid analgesia in the first 24 h of treatment, additional loading doses need to be considered.

© 2021. The Author(s).

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