Neonatal pharmacology and clinical implications

Abstract

During the neonatal period, there is physiological immaturity of organs, systems and metabolic pathways that influences the pharmacokinetics and pharmacodynamics of administered drugs, the dosage of which should be constantly amended, considering the progressive increase in weight and the maturation of the elimination pathways. In this article, we analyse the main pharmacokinetic aspects (absorption, distribution, metabolism and excretion) that exist during the neonatal period, to offer a description of the physiological background for variability in pharmacological dosing.

Therapeutic Drug Monitoring Is a Feasible Tool to Personalize Drug Administration in Neonates Using New Techniques: An Overview on the Pharmacokinetics and Pharmacodynamics in Neonatal Age

“…Compared to adults, neonates have lower concentrations of most plasma binding proteins (e.g., albumin, α1-acid glycoprotein, or plasma globulins). Furthermore, in newborns, an increase of concentrations of bilirubin and free fatty acids could be observed, and this can result in a competitive binding of the drugs to albumin [12,13].…”

“…However, developmental changes are dynamic processes: this physiological characteristic of neonates can lead to therapeutic failures and unsafe side effects during the therapy [24]. Moreover, there are many interactions between genetic factors, which influence pharmacokinetics and pharmacodynamics (e.g., genetic polymorphisms of cytochrome CYP2C19 that influence metabolism of benzodiazepines and proton pump inhibitors), as well as environmental factors (e.g., a still ongoing nephrogenesis, eventual malformations or injuries and the administration of concomitant drugs, especially in preterm neonates) [13].…”

Transplacental Passage and Fetal Effects of Antineoplastic Treatment during Pregnancy

“…In the first ten days after conception embryonal cells are omnipotent and the "all-or-nothing" phenomenon is observed, after the exposure to a toxic drug the embryo survives if few cells are destroyed, while it dies when the number of destroyed cells is elevated [10]. The administration of antineoplastic drugs is contraindicated from 10 days after conception and until 14 weeks of pregnancy because of the elevated risk of major malformations (to the hearth, neural tube, upper and lower limbs, eyes, palate and ears) that may occur during the organogenesis [11]. After the first trimester, the administration of chemotherapy carries an increased risk of preterm birth, intrauterine growth restriction (IUGR), low birth weight and bone marrow suppression, but also of minor anomalies and functional defects for eyes, gonads and genitalia, hematopoietic system and central nervous system [12].…”

Inhaled Pharmacotherapy for Neonates: A Narrative Review

“…Pharmacokinetics and pharmacodynamics exhibit considerable interindividual variability among neonates. 12 Because of the limited data and the absence of rigorous tests in neonates, these drugs are often used off-label. The inhaled route offers several significant advantages over the systemic routes of drug administration, since it delivers medication directly to the diseased organ, enabling higher doses locally with less systemic toxicity, and more rapid onset of action.…”