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Please use this identifier to cite or link to this item: http://hdl.handle.net/1807/27579

Title: Development of Novel Methodologies for the Evaluation of Fetal and Pediatric Drug Exposure
Authors: Garcia Bournissen, Facundo
Advisor: Koren, Gideon
Department: Medical Science
Keywords: pediatric clinical pharmacology
hair testing
placental drug transfer
population pharmacokinetics
breast milk
infant drug exposure
Chagas disease
Issue Date: 9-Jun-2011
Abstract: Passive exposure of children to drugs is common, but difficult to ascertain as direct studies are in many cases not possible, and currently available indirect measures of drug exposure, such as maternal reports, are likely to be inaccurate. Novel, indirect methods to evaluate drug exposure in the uterus and early life are needed, and may provide risk estimates that can be later correlated with clinical outcomes. In the studies presented here, I have applied novel methods such as measurement of hair drug concentrations and population pharmacokinetics modeling and simulation to evaluate fetal and infant exposure to drugs and potential associated risks. Testing for methamphetamine allowed demonstration, for the first time, that it freely crosses the human placenta. In contrast, analysis of paired maternal–infant hair showed limited cocaine placental transfer, in agreement with animal models. Results of hair tests from children found in marihuana grow houses and other drug operations showed that passive exposure tends to be higher in infants, likely due to higher dependence on, and proximity to care givers. We also demonstrated the importance of measuring drug metabolites to distinguish between systemic exposure to MDMA and simple external hair contamination secondary to drug present in the home environment. Finally, we developed a population pharmacokinetics and simulation approach to accurately estimate drug excretion into breast milk. This novel technique was applied to fluoxetine and to nifurtimox. Use of our approach allowed us to define, for the first time, the limited extent to which fluoxetine and nifurtimox would be expected to cross into breast milk and estimate potential degree of exposure of breastfed infants. In summary, results presented here support the value of these novel methods for the evaluation of fetal and infant drug exposure and suggest a promising value in estimating risks to children passively exposed to drugs.
URI: http://hdl.handle.net/1807/27579
Appears in Collections:Doctoral

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