Browsing Pharmaceutics by Title
Now showing items 48-67 of 80
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Mathematical Models to Evaluate the Clinical and Economic Impact of Biomedical HIV Prevention Strategies in the United States
As the marginal clinical impact returns on innovations to treat and prevent HIV diminish, strategic investments are required for timely and efficient HIV eradication. The overall goal of this dissertation research is to ... -
Mechanistic Physiologically Based Pharmacokinetic (PBPK) Modeling of Renal and Systemic Disposition of Drugs and Metabolites
Physiologically-based pharmacokinetic (PBPK) models integrate system specific anatomy and physiology information with drug specific physicochemical and pharmacokinetic properties to predict drug disposition. Such integration ... -
Metabolic and inhibitory differences between cytochromes P450 3A4 and 3A5
(2001)Cytochrome P450 (CYP) 3A4 and 3A5 constitute the dominant drug metabolizing enzymes in the liver and small intestine, and the content and activity of these enzymes is widely variable. Accurate knowledge of in vivo CYP3A ... -
Migraine-specific health resource utilization in chronic and episodic migraine across six countries
(2012-09-13)Background: Though studies have consistently revealed variation in resource utilization between chronic and episodic migraineurs, less is known about how these differences compare across countries. This research describes ... -
Molecular and Cellular Characterization of Human Embryonic Stem Cell Derived Hepatocytes
Primary human hepatocytes are commonly used to evaluate liver drug metabolism and toxicity. Pluripotent stem cell derived hepatocytes (SCDHs) have the potential to overcome access and function-related limitations associated ... -
Molecular Mechanisms of Drug Transport at the Blood-CSF Barrier Revealed by Live Tissue Imaging and Quantitative Fluorescence Microscopy
The blood-cerebrospinal fluid barrier (BCSFB) is formed by the choroid plexus epithelial (CPE) cells, which express several polyspecific membrane transporters that contribute towards clearance of xenobiotic and endogenous ... -
Of Mice and Women: Understanding Pregnancy-Induced Changes in Glyburide PK/PD for the Improved Management of Gestational Diabetes Mellitus (GDM)
Pregnancy-induced changes in drug PK is explained by changes in physiology and expression of metabolic enzymes and transporters. We determined mRNA expression of enzymes and transporters in the maternal liver, kidney, small ... -
Pharmacokinetics and Physiologically Based Pharmacokinetic Modeling of Xenobiotic Disposition in Special Populations
Due to the alteration of the physiological functions, the disposition of xenobiotics is often changed under disease conditions and during pregnancy compared with the healthy status. Under disease conditions including chronic ... -
Precision Approaches for Assessing Complex Pharmacogenomic Traits in Vitamin K Metabolism
The term “gene-environment interaction” accounts for various ways in which the effects of environmental exposures can be modified by our genetic variation. Of particular interest for this dissertation is the CYP4F2*3 coding ... -
Predicting Drug Disposition during Pregnancy through Modeling and Simulation
(2013-07-23)Physiological and ADME changes during pregnancy can significantly affect drug pharmacokinetics and may necessitate dose adjustment. Since it is logistically impossible to delineate the changes in PK of all drugs administered ... -
Predicting Human Fetal Drug Exposure to Placental P-glycoprotein Substrates by PBPK Modeling and Simulation
More than 80% of pregnant women take at least one drug during pregnancy and about 50% during the first trimester when the fetus is the most vulnerable to drug toxicity (Scaffidi, Mol, & Keelan, 2017). To inform fetal risk ... -
Predicting maternal-fetal cannabinoid exposure during pregnancy using physiologically-based pharmacokinetic modeling and simulation
Maternal marijuana (cannabis) use during pregnancy is associated with reduced fetal growth and subtle but persistent neurodevelopmental effects. It is not possible to establish the independent risk associated with maternal ... -
Predicting Maternal-Fetal Disposition of Drugs Using In Vitro and In Silico Tools
During pregnancy, physiological and ADMET changes in the maternal-fetal dyad can significantly alter drug pharmacokinetics (PK) in the mother and may necessitate dosing regimen adjustments. One clinically important example ... -
Prediction of in vivo metabolite disposition and complex metabolite-dependent drug-drug interactions
(2013-07-25)Metabolites can have pharmacological or toxicological effects, inhibit metabolic enzymes and be used as probes of drug-drug interactions or specific cytochrome P450 phenotypes. Thus better understanding and prediction ... -
Prediction of Transporter-Based Drug Clearances and Tissue Concentrations: Relative Expression Factor Approach and Protein-Mediated Uptake Effect
Clinical drug development often fails due to insufficient efficacy and safety, which can be attributed to not reaching the desired drug concentrations at their target sites (Smietana et al., 2016).Therefore, for successful ... -
Quantification and Prediction of Human Fetal (-)-Δ9-tetrahydrocannabinol (THC)/11-OH-THC Exposure to Inform Neurodevelopmental Toxicity of Cannabis
Prenatal cannabis use is associated with various detrimental outcomes in the offspring, the foremost being neurodevelopmental toxicity1-5. Δ9-tetrahydrocannabinol (THC) is the most abundant psychoactive compound in cannabis ... -
The Relative Importance of CYP26A1 and CYP26B1 in Mediating Retinoid Homeostasis: Studies on the Formation, Elimination and Biological Activity of All-trans-Retinoic Acid Metabolites
(2013-07-25)All-trans-retinoic acid (atRA), the active metabolite of Vitamin A (retinol), is an essential nutrient during both fetal development and adult life. The concentration of atRA within a cell is tightly regulated by the ... -
Renal Drug Transporters – Clinical Significance and Role in Drug-Drug Interactions
Drug transporters play an important role in drug disposition and can be major determinants of drug pharmacokinetics, pharmacodynamics and toxicity. In contrast to drug metabolizing enzymes, which mainly concentrate in the ... -
Renal Tubular Transport of Drugs in Healthy and Diseased Kidney
In this thesis work, I applied traditional and innovative bioengineering approaches to develop an in vitro model of renal proximal tubule with human proximal tubule epithelial cells (PTECs) that is particularly suited for ...