Thesis (MAppSc in Pharmacy)--University of South Australia, 1995

Thesis (MAppSc in Pharmacy)--University of South Australia, 1995

This thesis examines the effects of continuous theophylline pretreatment on the A$ sb2$ adenosine receptor system in cultured murine neuroblastoma cell lines, which either do or do not also express A$ sb1$ adenosine receptors. N-Ethylcarboxamido adenosine (NECA) stimulates cAMP accumulation and binds to A$ sb2$ receptors in a saturable and biphasic fashion in both types of cell cultures. Sixteen hours of theophylline treatment led to a significant increase in the number of low affinity A$ sb2$ binding sites, as well as a potentiation of NECA-stimulated cAMP accumulation, regardless of whether the cells expressed A$ sb1$ receptors. The enhanced adenylate cyclase stimulation in cells treated for 8 hours is completely blocked by addition of cycloheximide, indicating that new protein synthesis plays a role in the effects of theophylline. The potentiated response to NECA continues through 1 week of treatment in both sets of cultured cells, but disappears after 2 weeks of theophylline pretreatment in the cells expressing both A$ sb1$ and A$ sb2$ receptors. Binding profiles in cells that do not express A$ sb1$ receptors demonstrate that while control cells are sensitive to the effects of the non-hydrolyzable analogue of guanosine triphosphate, Gpp(NH)p, cells that were treated for 4 days or 1 week with theophylline are no longer sensitive to the effects of this compound. This could indicate either an enhanced coupling between the receptor and the stimulatory guanine nucleotide regulatory protein (G$ rm sb{s}$ protein) or a complete uncoupling of these two proteins. There is a significant decrease in the basal cAMP levels after 4 days or more of treatment, as well as an increase in the immunoreactivity of the $ alpha$ subunit of the stimulatory G protein after 2 weeks of treatment. Taken together, these findings would tend to favour the possibility of enhanced coupling between the receptor and the G$ rm sb{s}$ protein. Cells that express both receptor subtypes also show

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Thesis (Ph. D.)--University of Washington, 2003. / Vita. Includes bibliographical references (leaves 179-188).

Effects of age, dosage regimen, dose level, and routes of administration on the pharmacokinetics of acrylamide (ACR) and theophylline (TP) in Fischer 344 rats have been studied. ACR treatment consisted of administration of a single subtoxic dose or of multiple doses known to induce neurotoxicity to 5 and 11 week old rats. The effects of age and dosing regimen on the determination of pharmacokinetic parameters were studied. Multiply dosed rats had significantly longer plasma half lives than the singly dosed animals. Clearance values in the plasma were also significantly decreased following multiple dosing. Animals treated with TP received a single dose at different dose levels either intravenously or orally. No statistical difference was found between beta, Vbeta , and Cl based on dose level. All pharmacokinetic parameters were similar in magnitude to literature values for humans. Following oral dosing, plasma levels of TP were constant for the duration of the experiment. (Abstract shortened with permission of author.)

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A Dissertation Submitted to the Faculty of Medicine, University of the Witwatersrand, Johannesburg for the Degree of Master of Pharmacy. Johannesburg, August 1991 / In this dissertation physicochemical properties of the Bs vitamer, pyridoxal hydrochloride (PL HC1), are investigated with the aim of generating the necessary profile for the rational development of a stable, safe and effective formulation containing this drug. Recent research suggests that administration of PL HC1 may be particularly effective in raising the depleted intracellular pyridoxal phosphate levels found in many asthmatics treated with theophylline. The solubility characteristics of PL HC1 suggest that its absorption and bioavailability should not be problematic / IT2018

Thesis (Ph. D.)--University of Washington, 2001. / Vita. Includes bibliographical references (leaves 126-139).