Mathematical Albumin Function for Neonates Undergoing Therapeutic Hypothermia in Comparison with Control Neonates

2025-02-11

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.

dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_being; name=SDG 3 - Good Health and Well-being; article

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QGQ oai:pure.eur.nl:publications/4465423f-6826-48d5-bfe8-c124c2cd296f
https://pure.eur.nl/en/publications/4465423f-6826-48d5-bfe8-c124c2cd296f
https://doi.org/10.1002/jcph.70003
https://pure.eur.nl/ws/files/186811827/Mathematical_Albumin_Function_for_Neonates_Undergoing_Therapeutic_Hypothermia_in_Comparison_with_Control_Neonates.pdf
1510696758

ERASMUS UNIVERSITEIT ROTTERDAM
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