The Effect of Asphyxia on the Pharmacokinetics of Ceftazidime in the Term Newborn

Anker, John N. van den; Heijden, Bert J. van der; Hop, Wim C. J.; Schoemaker, Rik C.; Broerse, H. M.; Neijens, H. J.; Groot, Ronald de

doi:10.1203/00006450-199511000-00028

Cited by 15 publications

(7 citation statements)

References 12 publications

(10 reference statements)

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“…Probably, due to the background, some other reports also used a relatively small number (approximately 20 cases) of patients with asphyxia [23,40] .…”

Section: Discussionmentioning

confidence: 99%

Elevation of Cytokine Concentrations in Asphyxiated Neonates

et al. 2006

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Background: Various cytokines are reportedly associated with many neonatal diseases. Asphyxia is considered to result in ischemia-reperfusion injuries and induces abnormal inflammatory responses involving excessive cytokine production. Objectives: To evaluate alteration in sera levels of various cytokines/chemokines in case of perinatal asphyxia at birth. Methods: In orderto determine the concentrations of various cytokines/chemokines in sera, we used a highly sensitive fluorescence microsphere method. We measured the concentration of 8 types of cytokines/chemokines in sera obtained from 17 cases of asphyxia, 10 normal neonates, and 6 healthy adults. Results: The concentrations of IL-6, IL-8, and IL-10 in the sera of asphyxiated neonates were higher than those in the normal neonates. Irrespective of the presence or absence of asphyxia, sera concentrations of IL-2, IL-4, IFN-γ, and TNF-α were higher in the neonates than those in the adults. The concentration of IFN-γ in the asphyxiated neonates was lower than that in the normal neonates. Sera levels of IL-10 were higher in the asphyxiated cases than those in the normal neonates. The sera levels of IL-6, IL-8, and IL-10 in asphyxiated neonates with either a poor outcome or death were higher than those without poor outcomes. Conclusions: The concentrations of various types of cytokines/chemokines were different in neonatal sera and some of them increased drastically during asphyxia. The concentration of an anti-inflammatory cytokine IL-10 was elevated in asphyxiated neonates immediately after birth, thereby suggesting that IL-10 might be associated with neuroprotective functions.

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“…Probably, due to the background, some other reports also used a relatively small number (approximately 20 cases) of patients with asphyxia [23,40] .…”

Section: Discussionmentioning

confidence: 99%

Elevation of Cytokine Concentrations in Asphyxiated Neonates

et al. 2006

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“…To further illustrate this, critical illness associated with inflammation results in down regulation of DMEs [27]. Perinatal asphyxia results in a decrease in renal function in neonates up to 40-50% [29,30]. Furthermore, the status of the ductus arteriosus (open/closed) has an impact on both clearance and volume of distribution.…”

Section: Changes In Drug Metabolism: Enzyme Maturation and Non-maturamentioning

confidence: 99%

Drug metabolism in early infancy: opioids as an illustration

Donge

Mian

Tibboel

et al. 2018

Expert Opinion on Drug Metabolism & Toxicology

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Drug dosing in infants frequently depends on body weight as a crude indicator for maturation. Fentanyl (metabolized by Cytochrome P450 3A4) and morphine (glucuronidated by UDP-glucuronosyltransferase-2B7) served as model drugs to provide insight in maturation patterns of these enzymes and provide understanding of the impact of non-maturational factors to optimize dosing in infants. Areas covered: Systematic searches on metabolism and population pharmacokinetic (Pop-PK) models for fentanyl and morphine were performed. Pre- and post-model selection criteria were applied to assess and evaluate the validity of these models. It was observed that maturational changes have been rather well investigated, be it with variability in the maturational function estimates. The same holds true for Pop-PK models, where non-maturational covariates have also been reported (pharmacogenetics, disease state or external influences), although less incorporated in the PK models and with limited knowledge on mechanisms involved. Expert opinion: PK models for fentanyl and morphine are currently available. Consequently, we suggest that researchers should not continue to develop new models, but should investigate whether collected data fit in already existing models and provide additional value concerning the impact of (non)-maturational factors like drug-drug interactions or pharmacogenetics.

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“…In general, asphyxia may induce changes in drug disposition, such as reduced or altered drug absorption, increased or unchanged volume of distribution, and decreased drug clearance [ 173 , 174 ]. For example, the elimination of the serum half-life and serum trough concentrations of ceftazidime were significantly increased in asphyxiated neonates, whereas the clearance and GFR of ceftazidime decreased [ 175 ]. Another study based on a popPK model found that gentamicin clearance was significantly reduced in asphyxiated neonates compared to that in non-asphyxiated neonates, and a prolonged dosing interval was necessary to achieve target trough concentrations in this subpopulation [ 176 ].…”

Section: Resultsmentioning

confidence: 99%

Physiologically Based Pharmacokinetic Modeling in Neonates: Current Status and Future Perspectives

Zhang,

Cao

et al. 2023

Pharmaceutics

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Rational drug use in special populations is a clinical problem that doctors and pharma-cists must consider seriously. Neonates are the most physiologically immature and vulnerable to drug dosing. There is a pronounced difference in the anatomical and physiological profiles be-tween neonates and older people, affecting the absorption, distribution, metabolism, and excretion of drugs in vivo, ultimately leading to changes in drug concentration. Thus, dose adjustments in neonates are necessary to achieve adequate therapeutic concentrations and avoid drug toxicity. Over the past few decades, modeling and simulation techniques, especially physiologically based pharmacokinetic (PBPK) modeling, have been increasingly used in pediatric drug development and clinical therapy. This rigorously designed and verified model can effectively compensate for the deficiencies of clinical trials in neonates, provide a valuable reference for clinical research design, and even replace some clinical trials to predict drug plasma concentrations in newborns. This review introduces previous findings regarding age-dependent physiological changes and pathological factors affecting neonatal pharmacokinetics, along with their research means. The application of PBPK modeling in neonatal pharmacokinetic studies of various medications is also reviewed. Based on this, we propose future perspectives on neonatal PBPK modeling and hope for its broader application.

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The Effect of Asphyxia on the Pharmacokinetics of Ceftazidime in the Term Newborn

Cited by 15 publications

References 12 publications

Elevation of Cytokine Concentrations in Asphyxiated Neonates

Elevation of Cytokine Concentrations in Asphyxiated Neonates

Drug metabolism in early infancy: opioids as an illustration

Physiologically Based Pharmacokinetic Modeling in Neonates: Current Status and Future Perspectives

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