http://hdl.handle.net/1957/17743 2013-06-15T09:30:06Z http://hdl.handle.net/1957/39168 Comparison of pharmacokinetic data analysis with two competing pharmacokinetic software program Karnpracha, Chanida Pharmacokinetics (PK) is the study of the transit of drug into, within and removal from the body to reveal how the body acts on a drug when it is taken. There are four major areas in PK: absorption, distribution, metabolism and elimination. Pharmacokinetics research can be separated into two areas: clinical research and analysis of pharmacokinetics values. Upon obtaining drug concentrations at each sample time point, computer analysis using pharmacokinetics software is performed to determine the pharmacokinetics values of the drug: T[subscript max] (time to peak drug plasma concentration), C[subscript max] (peak plasma drug concentration), V (volume of distribution), half-life (t1/2), elimination constant (k) etc. Current pharmacokinetic software on the market includes programs such as WinNonlin, Kinetica, Pharmod, NONMEM. In this thesis, WinNonlin and Kinetica are used to analyze plasma drug concentrations versus time data sets to compare and validate the results of both software packages. There are two drug models used in this study, xanthohumol and lipoic acid. Xanthohumol (XN) is the most common flavonoid component found in hops, totaling about 82-89% of the amount of prenylated flavonoids present. However, there are other prenylflavonoids, isoxanthohumol (IX) and 8-prenylnaringenin (8PN). Isoxanthohumol (IX) can occur during the brewing process. The content of xanthohumol and isoxanthohumol depends on brewing conditions. 8-prenylnaringenin is produced by O-demethylation of isoxanthohumol. In this study xanthohumol was given in 20, 60 or 80 mg doses to healthy volunteers. After xanthohumol administration the plasma concentrations of xanthohumol increased rapidly with all three doses and reached the peak concentrations in 0.78, 1.23 and 2.03 hours for 20, 60 and 180 gm dose of xanthohumol, respectively. Xanthohumol and its metabolites were eliminated in 1, 2 or 3 days. Moreover there was linearity in the pharmacokinetics of xanthohumol as shown in the C[subscript max] versus dose curve, R² is 1. Isoxanthohumol was also formed rapidly from xanthohumol. T[subscript max] are 7 and 5 hours for medium and high dose respectively. Xanthohumol and isoxanthohumol each have a high volume distribution. Unfortunately, no results for 8-prenylnaringenin (8PN) were obtained due to plasma drug concentrations being undetectable in all subjects. Lipoic acid (LA) is also known as alpha lipoic acid or thioctic acid. It has two enantiomers, (R)-(+)-lipoic acid (RLA) and (S)-(-)-lipoic acid (SLA). A racemic mixture (R/S)-lipoic acid (R/S-LA) is commercially available. R-form of lipoic acid occurs naturally in food but the synthetic product is a racemic mixture. Lipoic 500mg in R- and racemic forms were given to healthy volunteers. Lipoic acid is absorbed rapidly in both forms, 40 minutes for racemic form and 30 minutes for R-form. The C[subscript max] and AUC values of racemic form are comparable to the R-form, around 2400 ng/mL for Cmax and 115,000 min*(ng/mL) for AUC. Comparing the results obtained on the pharmacokinetic parameters from the two pharmacokinetic software, Kinetica and WinNonlin revealed that almost all pharmacokinetic parameters of xanthohumol and isoxanthohumol obtained from Kinetica and WinNonlin are the same. However for the pharmacokinetic parameters of lipoic acid, all parameters are different, p-value <0.05, except for C[subscript max] and T[subscript max]. The comparisons of pharmacokinetic parameters show that only the normal data set of xanthohumol and isoxanthohumol produced the same results from Kinetica and WinNonlin software programs. The pharmacokinetic results obtained from pharmacokinetic programs vary due to the different methods of calculation and variations and limitations of the two programs. Graduation date: 2013 2013-05-16T00:00:00Z http://hdl.handle.net/1957/38706 Proteins Secreted via the Type II Secretion System: Smart Strategies of Vibrio cholerae to Maintain Fitness in Different Ecological Niches Sikora, Aleksandra E. No abstract available. This is the publisher’s final pdf. The published article is copyrighted by Public Library of Science and can be found at: http://www.plos.org/. 2013-02-21T00:00:00Z http://hdl.handle.net/1957/38581 Nanostructured Lipid Carriers as Multifunctional Nanomedicine Platform for Pulmonary Co-Delivery of Anticancer Drugs and siRNA Taratula, Oleh; Kuzmov, Andriy; Shah, Milin; Garbuzenko, Olga B.; Minko, Tamara We developed, synthesized, and tested a multifunctional nanostructured lipid nanocarrier- based system (NLCS) for efficient delivery of an anticancer drug and siRNA directly into the lungs by inhalation. The system contains: (1) nanostructured lipid carriers (NLC); (2) anticancer drug (doxorubicin or paclitaxel); (3) siRNA targeted to MRP1 mRNA as a suppressor of pump drug resistance; (4) siRNA targeted to BCL2 mRNA as a suppressor of nonpump cellular resistance and (5) a modified synthetic analog of luteinizing hormone- releasing hormone (LHRH) as a targeting moiety specific to the receptors that are overexpressed in the plasma membrane of lung cancer cells. The NLCS was tested in vitro using human lung cancer cells and in vivo utilizing mouse orthotopic model of human lung cancer. After inhalation, the proposed NLCS effectively delivered its payload into lung cancer cells leaving healthy lung tissues intact and also significantly decreasing the exposure of healthy organs when compared with intravenous injection. The NLCS showed enhanced antitumor activity when compared with intravenous treatment. The data obtained demonstrated high efficiency of proposed NLCS for tumor-targeted local delivery by inhalation of anticancer drugs and mixture of siRNAs specifically to lung cancer cells and, as a result, efficient suppression of tumor growth and prevention of adverse side effects on healthy organs. 2013-04-28T00:00:00Z http://hdl.handle.net/1957/38266 The Capacity Ratio as a Measure of Solvency in Experiential Education Danielson, Jennifer; Ramirez, Juancho; Krueger, Janelle; Christensen, Lindsay; Harshberger, Cara A.; Rice, Luke; Hudgins, Gayle A.; Weber, Stanley Objective. To determine the utility of the capacity ratio to measure and compare solvency in experiential education in 6 colleges and schools of pharmacy in the Northwestern United States. Methods. The 6 colleges and schools of pharmacy combined data on student placements needed, site availability, and changes made to placements during the 2009-2010 and 2010-2011 academic years and calculated capacity ratios for the advanced and introductory experience programs in the region. Comparisons also were made to previously published capacity results to determine whether the capacity ratio was useful in identifying trends and guiding preceptor and site development. Results. Capacity ratio calculations were successful in facilitating comparison of capacity within and across regions. Experiential education is solvent in the Northwest overall, but specific parts of experiential programs were found to have more capacity than others. Trends in the Northwest were consistent with capacity in other regions. Conclusions. The capacity ratio can determine and facilitate comparison of solvency within and across colleges and schools of pharmacy and thereby inform decisions about resource management in experiential education. This is the publisher’s final pdf. The published article is copyrighted by the American Association of Colleges of Pharmacy (AACP) and can be found at: http://www.ajpe.org/. 2011-12-15T00:00:00Z