Musteata, Marcel Theses Advised
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Item Simultaneous determination of free concentration, total concentration, and plasma binding capacity of bioactive compounds(Albany College of Pharmacy and Health Sciences Theses, 2020-09) Cibotaru, Dorina '20Free drug concentrations are well regarded as superior markers of pharmacological effect compared to total drug concentrations but are not used as often. Additionally, understanding drug-protein binding relationships is important for preclinical predictions of drug toxicity in humans and distribution into tissues. The current methods used for the determination of free concentration and drug-protein binding are limited to research or reference labs due to time constraints and availability of specialized machinery. A new proposed experimental method uses isotopically labeled analogues added to a sample and can be used to calculate free and total compound concentration and plasma binding capacity. Another involves multiple sequential analysis of a sample and can be used to calculate the total compound concentration and plasma binding capacity from measured free compound concentrations. Free analytes are separated using microextraction and ultrafiltration devices and measured using mass spectrometry. Testosterone and phenytoin are used as reference compounds in determining free fractions and plasma binding capacity due to their wide-spread usage as pharmacotherapy and high protein binding (\342\211\24590%). The normalization of free concentrations from patient samples using individual protein concentration and amount of compound bound to each protein can be used to help with the interpretation of biomarker concentrations in cases of variable protein binding. Resulting accuracy of analyte recovery from human serum albumin, volunteer plasma, and volunteer human serum samples support the use of SpinTip devices for microextraction and the use of Centrifree devices for ultrafiltration based on analyte recoveries between 90 and 100%, using both. Normalized compound serum concentrations were calculated, and the use of these methods may provide more insight about collected patient data. Sensitivity and uncertainty analyses reveal LCMS analysis to be the largest source of input uncertainty when calculating initial total testosterone concentrations and plasma binding capacity. Results obtained with patient samples support the use of SpinTips (R2=0.9954) and Centrifree (R2=0.9325) devices with labeled analytes for analysis of testosterone concentrations. The accuracy from using SpinTip devices was superior and the method using isotopically labeled testosterone resulted in very good accuracy for patient plasma samples, supporting the use of this method for further clinical applications.Item Improving the Accuracy of Total Body Clearance Measurement(Albany College of Pharmacy and Health Sciences Theses, 2017) LaPorte, Brandon '17Purpose Studies have showed that by assuming arteriovenous drug concentrations are homogenous after intravenous (IV) bolus injection, the determination of total body clearance based on venous drug concentrations is often inaccurate. Therefore, this investigation seeks to identify current inaccuracies in clearance calculations and to find an approach for accurately determining the correct value of total body clearance (Cl). By knowing the actual value of Cl pharmacologists can better understand drug disposition and ultimately design better drug dosing regimens.Item Investigating Transdermal Delivery of Vitamin D3(Albany College of Pharmacy and Health Sciences Theses, 2013) Alsaqr, Ahmed Abdullah '13Vitamin D3 (cholecalciferol) is a fat soluble vitamin approved for the treatment of vitamin D deficiency. Transdermal delivery is proposed for this drug to overcome its poor and variable oral bioavailability. In this study, the effect of different penetration enhancers, such as oleic acid, dodecylamine, ethanol, oleic acid in propylene glycol, isopropyl myristate, octyldodecanol, and oleyl alcohol in propylene glycol were evaluated in vitro for delivery of vitamin D3 through polyamide filter, polydimethylsiloxane (PDMS) membrane, and pig skin. A diffusion cell was used to study the transdermal permeability of vitamin D3. The ointment containing oleic acid as chemical penetration enhancers did not significantly enhance the permeability through polyamide filter, polydimethylsiloxane membrane and pig skin compared to control. However, the formulation containing dodecylamine as a penetration enhancer improved the delivery of vitamin D3 for both the filter and the PDMS membranes, but failed to improve it for pig skin. Only dodecylamine significantly enhanced vitamin D3 penetration into the epidermis after the skin was pretreated with 50% ethanol.Item Measurement and interpretation of the plasma concentration of vitamin D and its metabolites(Albany College of Pharmacy and Health Sciences Theses, 2013) Donabella, Paul J. B. '13Recent research has shown the importance of vitamin D status in the body. Vitamin D deficiency has been associated with fractures, poor physical function, and cardiovascular disease. The main marker of vitamin D status is 25-hydroxyvitamin D, a metabolite measured in serum. There are problems with this measurement because once in circulation nearly 99% of 25-hydroxyvitamin D is bound to plasma proteins, altering the biological activity. Some populations have more or less plasma proteins depending on factors such as age, and disease state. The main objective of this research is to develop the first validated equations for normalizing the concentration of 25-hydroxy vitamin D. The central hypothesis is that the concentration of 25OHD can be normalized based on the plasma binding capacity of each individual. The normalized concentration is the concentration that would produce a similar pharmacodynamic effect in an individual with normal plasma protein binding.