This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Exposure of infants and consumers to drugs and environmental toxins through breast or cows'milk is an ongoing concern. There is a need for valid in vitro models to determine the rate and extent to which chemicals are excreted in milk and to study the mechanisms by which chemicals cross this epithelial barrier. Cultured bovine mammary epithelial monolayers (BME-UV) mounted in flow-through diffusion chambers are used to determine the flux of a range of drugs across the mammary epithelial monolayer, testing for, and quantifying, the contribution of carrier-mediated transport processes. The relationship between the drugs'permeability across the BME-UV monolayer and their milk clearance will be determined by conducting in vivo pharmacokinetic studies in lactating dairy cattle. Results from these studies are essential to determine if the BME-UV cell line is suitable as an in vitro model to study the excretion of xenobiotics through cows'milk. The results are also needed as a foundation for future molecular studies to compare the expression of drug transporters in vitro, in vivo and between species. Ultimately, the goal will be to refine the model through a combination of selecting appropriate cell lines and biotechnology so that a system is developed that accurately predicts in vivo outcomes for specific species of interest. Such a model offers the opportunity to conduct studies with the aim of identifying, assessing and mitigating risks to human health posed by exposure to potentially harmful xenobiotics through human and cow's milk.
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