Mathematical albumin function for neonates undergoing therapeutic hypothermia in comparison with control neonates

Vander Elst, Zoë, Stultjens, Thibault, Annaert, Pieter, Clarke, Paul, Iglesias-Platas, Isabel, Agathos, Elisabeth, Kaykı, Gozdem, Laenen, Annouschka, Yalçın, Nadir, Smits, Anne and Allegaert, Karel (2025) Mathematical albumin function for neonates undergoing therapeutic hypothermia in comparison with control neonates. Journal of Clinical Pharmacology. ISSN 0091-2700

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Abstract

Hypoxic-ischemic encephalopathy (HIE) resulting from perinatal asphyxia presents a substantial risk of mortality and long-term sequelae in neonates. Therapeutic hypothermia (TH) improves both short- and long-term outcomes in near-term/term neonates with moderate to severe HIE. While neonates with perinatal asphyxia and TH often require polypharmacy, the impact of both covariates on pharmacokinetics and pharmacodynamics is only partially described and quantified. In this pooled, multicenter retrospective study, longitudinal trends of human serum albumin (HSA, the major drug binding protein) and total protein (TP) concentrations in near-term/term neonates were described using linear mixed models and compared between cohorts (TH vs control neonates, and moderate vs severe HIE TH cases). A mathematical function for HSA concentrations in neonates with HIE undergoing TH was derived (AlbuCool function). The pooled dataset to estimate these functions contained 330 TH neonates and 425 controls with 1725 and 1415 HSA observations, respectively. The median (interquartile range) HSA concentration was 27.0 (23.0–31.0) g/L for the TH cohort, and 32.1 (28.4–35.7) g/L for the control cohort. Estimated mean HSA concentrations were significantly lower (P < .001) in TH compared to control cases, as well as in severe compared to moderate HIE cases (P < .001) over the first 7 postnatal days. The HSA function for neonates with HIE undergoing TH was: HSA (g/L) = 32.28 − 2.94 * PNA + 0.33 * PNA2 (PNA is postnatal age). The integration of this function in pharmacokinetic models holds the promise to improve the predictive performance of these models, and consequently, the pharmacotherapy of HSA-bound drugs in this vulnerable population.

Item Type:	Article
Additional Information:	Data Availability Statement: The data that support the findings of this study are available from the corresponding author upon reasonable request. Funding information: This research was funded by a Senior research grant from the Research Scientific Foundation-Flanders (FWO) - G0D0520N, I-PREDICT: Innovative Physiology-based pharmacokinetic model to pREdict Drug exposure In neonates undergoing Cooling Therapy, and by a KU CELSA research project (Central Europe Leuven Strategic Alliance, CELSA/24/022).
Uncontrolled Keywords:	sdg 3 - good health and well-being ,/dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_being
Faculty \ School:	Faculty of Medicine and Health Sciences > Norwich Medical School
Depositing User:	LivePure Connector
Date Deposited:	12 Feb 2025 09:30
Last Modified:	17 Feb 2025 01:19
URI:	https://ueaeprints.uea.ac.uk/id/eprint/98454
DOI:	10.1002/jcph.70003

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