Addenda and corrigenda inserted on verso of back end paper. Includes: Publications and communications to learned societies (p. 4-5). Bibliography: leaves 272-286. Examines the acute myocardial uptake of drugs, particularly perindoprilat and enalaprilat in humans. The uptake of these agents is examined, together with the haemodynamic, metabolic and biochemical effects. In particular, the impact of these agents on angiotensin and bradykinin peptides both within the heart and peripherally is described. The acute effects of a range of cardioactive drugs upon the left ventricular force-interval relationship is examined.

Errata pasted onto front end paper. / Bibliography: leaves 193-211. / xiv, 211 leaves : ill. ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Describes the development and application of an in vitro model used to investigate the cytoprotective effects of a whey-derived growth factor extract in reducing epithelial cell death caused by chemotherapy agents. / Thesis (Ph.D.)--University of Adelaide, Dept. of Physiology, 1998

Thesis (Ph. D.)--University of Hong Kong, 2006. / Title proper from title frame. Also available in printed format.

Thesis (Ph. D.)--University of Missouri-Columbia, 2007. / The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. Title from title screen of research.pdf file (viewed on December 20, 2007) Includes bibliographical references.

Thesis (Ph. D.)--University of Texas at Austin, 2006. / Vita. Includes bibliographical references.

In vivo research following ingesting of commercially available Lactobacillus tablets, which contain about 2X10⁶ cfu/tablet of Lactobacillus acidophilus and Lactobacillus bulgaricus cells in a dose of four tablets daily, showed serum lipoprotein concentrations did not change significantly. In order to increase the number of viable Lactobacillus bacteria after challenging in low pH solution (gastric fluid), enteric coating polymer was applied over dried calcium alginate beads containing Lactobacillus. Survival of Lactobacillus bacteria was generally higher from freeze dried calcium alginate beads compared to vacuum dried products. However, after pretreatment with simulated gastric fluid (pH = 1.5) for 2 hours, only the coated products from vacuum drying showed promising results. Lactobacillus bacteria were fully protected against gastric pH after formulating the bacteria inside mini-tablets which were coated with Eudragit L30D, an enteric coating polymer. Alginic acids are naturally occurring substances found only in the brown seaweeds. Alginic acid salts formed with most di-, and polyvalent metals are insoluble in water. The most common application of alginate precipitation in drug product formulation is based on insolubilization of alginate by addition of calcium salt. By altering the composition of calcium alginate, drug loading, enteric coating thickness, and sustained release coating thickness, the lag time for drug dissolution can be controlled. This formulation research provides oral dosage form design for targeted delivery of drug to any desired site in the gastrointestinal tract. Examples of site specific targeted delivery are given for Lactobacillus bacteria, ibuprofen, sulfasalazine, and 5-aminosalicylic acid. / Graduation date: 1991

Over 220 million people worldwide are diagnosed with diabetes and rising prevalence is reported in nearly all surveyed populations. Accordingly, the percentage of pregnancies affected by pre-existing type 1 or 2 diabetes or by diabetes that develops during pregnancy, called gestational diabetes mellitus (GDM), is also on the rise. Today, approximately 8% of all pregnancies are complicated by diabetes. Diabetes alters drug disposition mechanisms in non-pregnant subjects but the impact of diabetes on drug disposition in pregnancy has not been properly evaluated. Atypical drug disposition in pregnancy has implications for maternal and fetal health. Because liver tissue from pregnant women is not readily available, this thesis investigated drug disposition mechanisms primarily in a rat model of experimental GDM. This model consisted of administering streptozotocin, a diabetogenic toxin, to pregnant rats on gestational day 6. One key finding was that elevated circulating lipids in GDM rats competed with drugs (e.g., glyburide and saquinavir) for plasma protein binding so as to increase free drug concentrations. Another key finding was that important hepatic drug efflux transporters (e.g., Mdr1a/b) and metabolic enzymes (e.g., Cyp3a2 and Ugt1a1) were upregulated in GDM as a consequence of, most likely, enhanced nuclear receptor activity (e.g., pregnane X receptor upregulation). Upregulation of hepatic drug efflux transporters and metabolic enzymes, coupled with larger unbound drug fractions, would be expected to increase the hepatic clearance of many drugs. Consistent with this, in GDM, maternal and fetal exposure to the Mdr1 and Cyp3a2 substrate lopinavir was substantially lower than controls post-administration and data supporting enhanced lopinavir metabolite formation were obtained. Placental drug efflux transporters were also examined in this lopinavir study. Elevated placental Mdr1b and Bcrp expression was observed in GDM, which was associated with decreased fetal exposure to lopinavir (even after correcting for maternal unbound concentrations). Taken together, this thesis demonstrates that experimental GDM can significantly impact drug disposition by altering key drug disposition mechanisms. If confirmed in humans, this drug-disease interaction would need to be considered when atypical therapeutic outcomes occur in diabetic pregnancies. Data from experiments with human placentas, obtained from pregnancies complicated by insulin-managed diabetes, is included/discussed.

Over 220 million people worldwide are diagnosed with diabetes and rising prevalence is reported in nearly all surveyed populations. Accordingly, the percentage of pregnancies affected by pre-existing type 1 or 2 diabetes or by diabetes that develops during pregnancy, called gestational diabetes mellitus (GDM), is also on the rise. Today, approximately 8% of all pregnancies are complicated by diabetes. Diabetes alters drug disposition mechanisms in non-pregnant subjects but the impact of diabetes on drug disposition in pregnancy has not been properly evaluated. Atypical drug disposition in pregnancy has implications for maternal and fetal health. Because liver tissue from pregnant women is not readily available, this thesis investigated drug disposition mechanisms primarily in a rat model of experimental GDM. This model consisted of administering streptozotocin, a diabetogenic toxin, to pregnant rats on gestational day 6. One key finding was that elevated circulating lipids in GDM rats competed with drugs (e.g., glyburide and saquinavir) for plasma protein binding so as to increase free drug concentrations. Another key finding was that important hepatic drug efflux transporters (e.g., Mdr1a/b) and metabolic enzymes (e.g., Cyp3a2 and Ugt1a1) were upregulated in GDM as a consequence of, most likely, enhanced nuclear receptor activity (e.g., pregnane X receptor upregulation). Upregulation of hepatic drug efflux transporters and metabolic enzymes, coupled with larger unbound drug fractions, would be expected to increase the hepatic clearance of many drugs. Consistent with this, in GDM, maternal and fetal exposure to the Mdr1 and Cyp3a2 substrate lopinavir was substantially lower than controls post-administration and data supporting enhanced lopinavir metabolite formation were obtained. Placental drug efflux transporters were also examined in this lopinavir study. Elevated placental Mdr1b and Bcrp expression was observed in GDM, which was associated with decreased fetal exposure to lopinavir (even after correcting for maternal unbound concentrations). Taken together, this thesis demonstrates that experimental GDM can significantly impact drug disposition by altering key drug disposition mechanisms. If confirmed in humans, this drug-disease interaction would need to be considered when atypical therapeutic outcomes occur in diabetic pregnancies. Data from experiments with human placentas, obtained from pregnancies complicated by insulin-managed diabetes, is included/discussed.

The thesis work entails a bench-to-bedside translational research approach to the development of pediatric fixed dose combination of zidovudine/lamivudine/nevirapine (60/30/50mg) orally disintegrating tablets. A simple and cost-effective, direct compression method was used. Preformulation studies that included analytical and bio-analytical assay development, excipient selection and characterization of drug-excipient interaction for initial formulation were conducted. Response surface methodology was utilized to optimize the formulation in terms of disintegration time and crushing strength. Stable ODT tablet was developed with desired friability (< 1%), reasonable crushing strength, disintegration time (< 30sec) and other quality attributes such as potency and dissolution. An open label randomized two-way cross-over bioequivalence of the product (with approved IRBs), conducted in 24 healthy adult volunteers, indicated the product to be bioequivalent with the innovators. 90% C.I of the point estimates of PK parameters evaluated were in the range of 80-125% as specified by FDA. / Mylan School of Pharmacy and the Graduate School of Pharmaceutical Sciences; / Pharmaceutics / MS; / Thesis;

Thesis (M.A.) - Simon Fraser University, 2005. / Theses (School of Communication) / Simon Fraser University. Also issued in digital format and available on the World Wide Web.