Browsing by Subject "pharmacokinetics"
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Item Delivery and efficacy of targeted therapeutics and imaging agents for brain tumors(2018-11) Kim, MinjeeThe treatment of both primary and secondary brain tumors is a serious unmet medical need in the field of neuro-oncology. Despite advances in developing molecularly-targeted anti-cancer therapeutics in treating peripheral tumors, there is no effective therapeutic for brain tumors that demonstrated dramatic improvement in patient survival. One of the major reasons of having lack of efficacy in central nervous system may be related to the delivery of therapeutic agents across the blood-brain barrier (BBB). The BBB expresses various transporters as well as unique junctional proteins that selectively permeate molecules into the brain from systemic circulation. Many molecularly-targeted therapeutic agents are found to be substrates of these efflux transporters at the BBB including P-glycoprotein (P-gp) and Breast cancer resistance protein (Bcrp). The current dissertation examined the multiple challenges in the treatment of brain tumors including non-specific protein binding, brain distributional kinetics, and role of efflux transporters on the distribution of various molecules such as molecularly-targeted anti-cancer drugs and tumor imaging agents.Item Quantitative Methods for Evidence Building in Clinical Pharmacology and Pharmaceutical Outcomes Research(2021-05) Margraf, DavidA variety of methods are employed to build evidence in pharmacology and pharmaceutical outcomes research. Descriptive and inferential statistics are used to describe the data and generalize findings to populations. Regression models, propensity score adjustment, and meta-analysis extend upon the quantitative approach to building evidence. Topic areas in this dissertation include demonstrating the application of these methods to a comparison of three-factor prothrombin complex concentrate versus four-factor prothrombin complex concentrate for emergent warfarin reversal via a propensity score adjusted retrospective cohort study and a systematic review and meta-analysis to address clinical problems and improve health outcomes. Also presented are the pharmacokinetics of intravenous N-acetylcysteine, Cysteine, and Glutathione and the effect of N-acetylcysteine as a reducing agent in Parkinson’s disease and Gaucher disease. While quantitative methods help us explore, explain, and generalize from data, it is imperative to consider the clinical relevance of the findings. We found that four-factor prothrombin complex concentrate is preferred for emergent warfarin reversal. This is a finding is useful in real-world patient care. Also, increased N-acetylcysteine plasma concentrations and Glutathione redox ratio are related, which could be used to optimize dosing in future studies. These examples are described in detail as examples of applications of quantitative methods.