Pre- and Postnatal Maturation are Important for Fentanyl Exposure in Preterm and Term Newborns : A Pooled Population Pharmacokinetic Study
Wu, Yunjiao ; Völler, Swantje ; Flint, Robert B. ; Simons, Sinno H.P. ; Allegaert, Karel ; Fellman, Vineta LU
and Knibbe, Catherijne A.J.
(2022)
In Clinical Pharmacokinetics
61(3).
p.401-412
- 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... (More)
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® 7.4. 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.
(Less)
- author
- Wu, Yunjiao
; Völler, Swantje
; Flint, Robert B.
; Simons, Sinno H.P.
; Allegaert, Karel
; Fellman, Vineta
LU
and Knibbe, Catherijne A.J.
- organization
- publishing date
- 2022
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Clinical Pharmacokinetics
- volume
- 61
- issue
- 3
- pages
- 401 - 412
- publisher
- Adis International
- external identifiers
-
- pmid:34773609
- scopus:85119293355
- ISSN
- 0312-5963
- DOI
- 10.1007/s40262-021-01076-0
- language
- English
- LU publication?
- yes
- id
- 32597876-d603-45d2-bbe4-3d725d06d78e
- date added to LUP
- 2021-12-13 14:28:15
- date last changed
- 2024-04-06 15:11:58
@article{32597876-d603-45d2-bbe4-3d725d06d78e,
abstract = {{<p>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<sup>®</sup> 7.4. 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.</p>}},
author = {{Wu, Yunjiao and Völler, Swantje and Flint, Robert B. and Simons, Sinno H.P. and Allegaert, Karel and Fellman, Vineta and Knibbe, Catherijne A.J.}},
issn = {{0312-5963}},
language = {{eng}},
number = {{3}},
pages = {{401--412}},
publisher = {{Adis International}},
series = {{Clinical Pharmacokinetics}},
title = {{Pre- and Postnatal Maturation are Important for Fentanyl Exposure in Preterm and Term Newborns : A Pooled Population Pharmacokinetic Study}},
url = {{http://dx.doi.org/10.1007/s40262-021-01076-0}},
doi = {{10.1007/s40262-021-01076-0}},
volume = {{61}},
year = {{2022}},
}