Current Pharmaceutical Design - Volume 23, Issue 38, 2017

Background: Effective and safe pharmacotherapy in an individual neonate necessitates understanding the pharmacokinetic (PK) and pharmacodynamic (PD) properties of a specific drug together with the characteristics of this neonate. Methods: Developmental PK hereby provides estimates of the concentration-time profile. Multiple maturational, disease and treatment related differences can result in differences in Read More

Background: The development of appropriate pharmaceutical formulations for routine neonatal practice is challenging because of the developmental characteristics and the need for it to be specifically ageappropriate. This has led to wide use of extemporaneous formulations, which lack standardized procedures that can result in medication errors in clinical practice resulting in suboptimal efficacy and safety co Read More

Introduction: Therapeutic drug monitoring (TDM) refers to the interpretation of quantified drug concentrations in strategically timed samples of bodily fluids, with the aim to maximize therapeutic benefit, while minimizing toxicity. In essence, TDM criteria for neonates are similar to those for adults, but specific issues should be considered. This review focusses on the relevance of these specific issues: larger variability in phar Read More

Background: Historically, neonatal therapeutic interventions were derived from adult therapeutics, and tragedies resulting from this approach have demonstrated differences in the pathophysiologic and developmental processes between neonates and older patients. Over the past 3 decades, researchers and collaborative research networks have made progress in the systematic evaluation of neonatal therapies, yet most neon Read More

Background: β-lactams are among the most frequently prescribed antibiotics for the treatment of neonatal sepsis. Survival of extremely preterm neonates necessitates an improved understanding of how β-lactams should be used in this vulnerable population. Appropriate dosing regimens for neonates remain unclear. We reviewed available data on the pharmacokinetics (PK) of β -lactam drugs in neonates. Pharmacokinetic/ p Read More

Background: Intravenous paracetamol (acetaminophen) has not been licensed for analgesia in preterm neonates or infants < 2 years, respectively, in Europe and the United States. A variety of dosing regimens is therefore used off-label. Because evidence supports the use of the same target mean steady state paracetamol concentration (Cssmean, 9-11 mg/L) for pain relief in neonates compared to older children and adults, Read More

Background: Circulatory failure in preterm and term newborn infants is commonly treated with inotropes or vasoactive medications. In this structured literature review, the available data on pharmacodynamic effects of the inotropes adrenaline, dobutamine, dopamine, levosimendan, milrinone, noradrenaline, and the vasoactive drugs vasopressin and hydrocortisone are presented. Methods: Structured searches were Read More

Background: although neonatal pain management has seen huge improvements in the past years, many gaps between knowledge and practice still exist. Objective: to give the reader the state of the art of actual pain management and treatment. Methods: a literature review was done on the physiopathology of pain, sex differences in the perception of pain, epidemiology, non-pharmacological treatment and developmental ca Read More

Background Experimental studies have shown that neonatal exposure to stress, pain, opioids and anaesthetics may cause histologic and morphologic changes in the central nervous system with associated functional and behavioural changes in the long term. An important question is whether this holds true for humans also – and in particular for sick neonates who often are exposed to pain and receive anaesthetics an Read More

Bronchopulmonary dysplasia (BPD) remains a frequent and disabling consequence of preterm birth, despite the recent advances in neonatal intensive care. There is a need to further improve outcomes and many novel therapeutic or preventive strategies are therefore investigated in animal models. We discuss in this review the aspects of human BPD pathophysiology and phenotype, which ideally should be mimicked b Read More

Introduction: In the Neonatal Intensive Care Unit (NICU), prematurely born infants undergo a range of skin breaking and painful procedures. At the same time, the spinal nociceptive system is in a sensitive developmental stage. Both neonatal repetitive painful procedures and their treatment can induce plasticity of the neonatal spinal nociceptive system, causing long-lasting alterations to pain processing and pain reactivity. Metho Read More

Background: Finding the right drug-dosage for neonates is still a challenge. Until now, neonatal doses are extrapolated from adults and children doses. However, there are differences between neonatal and adult kidney physiology that should be considered, especially when it comes to drug metabolism and/or transport. Studying renal drug disposition in neonates is limited by the lack of reliable human cell models. Objective: Read More

Background: Drug effect evaluation is often based on subjective interpretation of a selection of patient data. Continuous analyses of high frequency patient monitor data are a valuable source to measuring drug effects. However, these have not yet been fully explored in clinical care. We aim to evaluate the usefulness and applicability of high frequency physiological data for analyses of pharmacotherapy. Methods: As a proof of p Read More

Background: Local delivery of drugs to the lungs of newborn infant represents an unmet need as no drugs have been approved. Potential benefits could be large. Development of aerosol for delivery of drugs to infants and newborn offers huge potential for better therapy. Newborn infants present unique challenges with regard to aerosol therapy. Efficient deposition of aerosolized medications on the neonate airway surface Read More

Background: Hypoxic-ischemic encephalopathy (HIE) is an important cause of neonatal mortality and neurological morbidity, even despite hypothermia treatment. Neuronal damage in these infants is partly caused by the production of superoxides via the xanthine-oxidase pathway and concomitant free radical formation. Allopurinol is a xanthine-oxidase inhibitor and can potentially reduce the formation of these superox Read More

Introduction: The neonatal population remains one of the populations in which appropriate dosing regimens are still lacking, resulting in a large off-label or unlicensed use. Clinical research in these small infants remains a challenge, which sparks the need for modeling and simulation as an additional tool for neonatal drug research. Methods: The use of physiologically based pharmacokinetic modeling in preterm and term ne Read More

Background: Drugs acting on the cardiovascular and central nervous system often display relatively fast clinical responses, which may differ in neonates compared to children and adults. Introduction of bedside monitoring tools might be of additional value in the pharmacodynamic (PD) assessment of such drugs in neonates. Methods: We aim to provide an overview of the frequently used monitoring tools to assess drug e Read More

Background: Insulin-like growth factor 1 (IGF-1) is a mitogenic hormone involved in many processes such as growth, metabolism, angiogenesis and differentiation. After very preterm birth, energy demands increase while maternal supplies of nutrients and other factors are lost and the infant may become dependent on parenteral nutrition for weeks. Low postnatal IGF-1 concentrations in preterm infants are associated with po Read More