Neonatal drug delivery and disposition: towards improving care for the youngest patients

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Title Neonatal drug delivery and disposition: towards improving care for the youngest patients
Publication Type dissertation
School or College College of Pharmacy
Department Pharmaceutics & Pharmaceutical Chemistry
Author Linakis, Matthew Wiliiam
Date 2018
Description Research in pediatric medicine has undergone a significant and beneficial transformation in the past several years. However, neonates (birth to 27 days of age) are still administered drugs off-label far too often, and there is a paucity of data supporting safe and effective use of many drugs in this population. The goal of this dissertation is to highlight areas in which neonatal pharmacological treatment is lacking and to detail studies that have been performed to begin filling those knowledge gaps. The first set of studies addressed the challenges associated with oral drug delivery in neonates. An extemporaneous liquid formulation of the steroid oxandrolone was developed for reduction of weight loss following surgery. While neonates cannot be treated with the tablet form of the drug, the liquid drug-in-oil formulation allows buccal administration. The formulation was characterized and determined to be stable for 28 days. Preliminary pharmacokinetic modeling performed on available plasma concentrations from 10 neonates demonstrated extensive variability in drug disposition. The second set of studies examined the appropriateness of transdermal drug delivery for neonates. To use most transdermal patches in such small patients, it becomes necessary to resize the patches to provide an appropriately reduced dose. Thus, two studies were performed to understand the variability in pharmacokinetics of a transdermal patch and the effects of transdermal patch cutting. The former study demonstrated that weight may be a significant factor on the transdermal kinetics of a drug, while the latter showed that patch cutting could reasonably be used to resize matrix-type patches. The final study considered the interplay of ontogeny and drug metabolism in neonates related to genetic variation. This study probed various genetic polymorphisms in drug metabolizing enzymes for their effect on acetaminophen disposition. Ultimately, it was determined that a T-insertion mutation in UGT1A9 was the greatest contributor to variability in the studied population of neonates. Overall, the studies pursued in this manuscript attempt to address various gaps currently present in neonatal research and medicine. Ideally, these studies represent important steps towards providing practicing physicians with a greater body of evidence to support treatment of the youngest of patients.
Type Text
Publisher University of Utah
Subject Pharmacology; Pharmaceutical sciences
Dissertation Name Doctor of Philosophy
Language eng
Rights Management (c) Matthew William Linakis
Format application/pdf
Format Medium application/pdf
ARK ark:/87278/s6kd711f
Setname ir_etd
ID 1525828
Reference URL https://collections.lib.utah.edu/ark:/87278/s6kd711f
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