Personalized Neonatal Medicine

Fanos, Vassilios; Yurdakök, Murat

doi:10.3109/14767058.2010.513103

Cited by 21 publications

(11 citation statements)

References 19 publications

(19 reference statements)

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“…The major challenge in neonates is however to maximize these concepts to result in a more efficacious treatment in the context of their immature distribution and excretion pathways, while still using dosing guidelines and precautions to avoid dosing errors: the balance between physiology and feasibility [31][32][33].…”

Section: Karel Allegaertmentioning

confidence: 99%

Dosing Guidelines of Aminoglycosides in Neonates: A Balance Between Physiology and Feasibility

Allegaert

Cossey²,

Anker³

2015

CPD

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Once daily dosing of aminoglycosides has been introduced and validated in non-neonatal patient cohorts. This is because aminoglycosides display peak concentration dependent bacterial killing, have a postantibiotic effect and adaptive resistance. In addition, this strategy reduces toxicity. Although aminoglycosides are also frequently administered to neonates, there is still debate about how to integrate and extrapolate these extended interval dosing regimens into dosing schedules tailored for neonates. There is a growing body of knowledge on aminoglycoside disposition and its covariates (e.g. asphyxia, ibuprofen or indomethacin exposure, serum creatinine, sepsis, dose accuracy) in neonates. In essence, integration of developmental physiology with clinical pharmacology unveils a discrepancy between aspects related to either body composition (higher distribution volume necessitates higher dose, to attain peak concentration) or to elimination clearance (lower renal clearance necessitates prolonged time interval between administrations). Such discrepancy can be solved by introducing more complex dosing guidelines (based on weight, postnatal age, serum creatinine, ibuprofen, asphyxia) in neonates. However, the introduction of more complex dosing guidelines should be balanced with its clinical feasibility. At least, there are reports that these more complex dosing guidelines result in a higher incidence of dosing errors. Besides errors in prescription, these errors also relate to the number of dilutions or manipulations needed before the prescribed dose can be administered. Since an integrated approach is needed, we discuss in this overview both the available pharmacokinetic data in support of the use of extended dosing regimens in neonates as well as the strategies suggested to reduce dosing errors.

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Section: Karel Allegaertmentioning

confidence: 99%

Dosing Guidelines of Aminoglycosides in Neonates: A Balance Between Physiology and Feasibility

Allegaert

Cossey²,

Anker³

2015

CPD

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“…National and international dosing guidelines are incomplete and inconsistent, resulting in inappropriate prescription of the majority of antibiotic agents in neonates. Furthermore, caregivers prescribe drugs to neonates that were developed for adults or older children by simply extrapolating doses based on body weight without accounting for dynamic maturation processes during the first weeks of life . As a result newborns remain the last therapeutic orphans …”

mentioning

confidence: 99%

Pharmacometric Approaches to Personalize Use of Primarily Renally Eliminated Antibiotics in Preterm and Term Neonates

Wilbaux

Fuchs

Samardžić

et al. 2016

The Journal of Clinical Pharma

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Sepsis remains a major cause of mortality and morbidity in neonates, and, as a consequence, antibiotics are the most frequently prescribed drugs in this vulnerable patient population. Growth and dynamic maturation processes during the first weeks of life result in large inter- and intrasubject variability in the pharmacokinetics (PK) and pharmacodynamics (PD) of antibiotics. In this review we (1) summarize the available population PK data and models for primarily renally eliminated antibiotics, (2) discuss quantitative approaches to account for effects of growth and maturation processes on drug exposure and response, (3) evaluate current dose recommendations, and (4) identify opportunities to further optimize and personalize dosing strategies of these antibiotics in preterm and term neonates. Although population PK models have been developed for several of these drugs, exposure-response relationships of primarily renally eliminated antibiotics in these fragile infants are not well understood, monitoring strategies remain inconsistent, and consensus on optimal, personalized dosing of these drugs in these patients is absent. Tailored PK/PD studies and models are useful to better understand relationships between drug exposures and microbiological or clinical outcomes. Pharmacometric modeling and simulation approaches facilitate quantitative evaluation and optimization of treatment strategies. National and international collaborations and platforms are essential to standardize and harmonize not only studies and models but also monitoring and dosing strategies. Simple bedside decision tools assist clinical pharmacologists and neonatologists in their efforts to fine-tune and personalize the use of primarily renally eliminated antibiotics in term and preterm neonates.

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“…Taken all together, it becomes apparent that children cannot be regarded as "small adults" with respect to drug therapy: they often need a different fraction of drug per Kg of body weight as compared to adults. For example as for digoxin, a drug excreted by glomerular filtration but also secreted by the tubular renal cell, newborns need threefold higher doses per Kg body weight than adults [39].…”

Section: Anatomo-functional Immaturity and Management Of Antibiotics mentioning

confidence: 99%

A Developmental Approach to Drug-induced Liver Injury in Newborns and Children

Faa

Ekström²,

Castagnola³

et al. 2012

CMC

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The liver represents the major site of drug metabolism in humans. The developmental changes that occur in the liver's metabolic activity during fetal life and in the perinatal period are at the basis of the varied sensitivity of human newborns to many drugs. The decreased capacity of the fetal and newborn liver to metabolize, detoxify, and excrete drugs--total cytochrome P450 content in the fetal liver being 30% to 60% of adult values--may explain the prolonged actions of many drugs in the newborn, as well as less their potential toxicity. On the other hand, the low levels of phase I (activation) enzymes, producing more polar reactive and often toxic metabolites, could explain the lower incidence of adverse effects of some drugs reported in newborns. Moreover, the greater capacity of newborns to synthesize glutathione is at the basis of their ability in inactivating many toxic metabolites. Here we review the acute and chronic liver toxicity due to the most widely used drugs in the neonate. We will discuss in detail the biochemical profile of the fetal and neonatal liver, and the toxic metabolites formed during the metabolism of the most widely used drugs in the neonate. The histological picture of liver disease related to the therapeutic use of drugs will be discussed, with particular emphasis on the mode of cell death involved in hepatitis induced by different drugs most frequently utilized in the neonatal intensive care units.

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Personalized Neonatal Medicine

Cited by 21 publications

References 19 publications

Dosing Guidelines of Aminoglycosides in Neonates: A Balance Between Physiology and Feasibility

Dosing Guidelines of Aminoglycosides in Neonates: A Balance Between Physiology and Feasibility

Pharmacometric Approaches to Personalize Use of Primarily Renally Eliminated Antibiotics in Preterm and Term Neonates

A Developmental Approach to Drug-induced Liver Injury in Newborns and Children

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