Thesis (Ph. D.)--University of Washington, 1984. / Vita. Includes bibliographical references.

Thesis (Ph.D.) -- University of Adelaide, Dept. of Physiology, 1982. / Typescript (photocopy).

Thesis (M. Phil.)--University of Hong Kong, 1990.

Thesis (Ph. D.)--Marshall University, 2003. / Title from document title page. Document formatted into pages; contains p. xii, 152 p. including illustrations. Includes abstract. Includes vita. Includes bibliographical references (p. 133-140).

Gastrointestinal (GI) transit data were collected using pigs as animal models. Density and size effects of non-disintegrating dosage forms on GI transit were investigated. Total GI transit times range from 2 to 33 days for 22 administrations of these nondisintegrating dosage forms. Pigs are found to not be an appropriate animal model for studying bioavailability or GI transit of non-disintegrating, non-erodible oral release dosage forms. Development of controlled release dosage forms where the mechanism of drug release is diffusion through polymeric membrane formed via film coating utilizing fluid-bed technology requires optimization of several processing and formulation variables. The influence of a processing variable (nozzle orifice opening) and a few formulation variables (individual vs. combination plasticizer, or a water-insoluble additive) on dissolution of a model drug (acetaminophen) spray coated with Aquacoat® were studied. Pharmacodynamic and pharmacokinetic information for a model drug (acetaminophen) and computer simulation were used to develop a dosage form with a 12 hour sustained release for oral administration to children and adults for maximum analgesic and antipyretic effect. Simulated plasma acetaminophen concentration-time curves were similar to observed bioavailability study profiles. In vitro and preliminary in vivo results from an adult human volunteer indicate that sustained therapeutic saliva acetaminophen concentration is possible using the newly developed acetaminophen molded tablet dosage form. The bioavailability of the new, oral controlled release acetaminophen molded tablet relative to a commercially available product (Extra-Strength Tylenol® caplet) was evaluated in 8 healthy, adult volunteers. Multiple doses of these two products were administered in a two-way cross-over design. Bioavailability of the new sustained release molded tablet is comparable to that of the immediate release product. Polymer coated acetaminophen beads were effective in maintaining saliva acetaminophen concentrations of 5 μ/ml over a 12 hour dosing interval. / Graduation date: 1991

Typescript (photocopy) / v, 94 leaves, [49] leaves of ill. : ill. ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (Ph.D.)--University of Adelaide, Dept. of Physiology, 1982

Typescript (photocopy) / v, 94 leaves, [49] leaves of ill. : ill. ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (Ph.D.)--University of Adelaide, Dept. of Physiology, 1982

Thesis (Ph. D.)--West Virginia University, 1999. / Title from document title page. Document formatted into pages; contains ix, 137 p. : ill. Vita. Includes abstract. Includes bibliographical references (p. 115-134).

There are few examples of therapeutic treatments in chemically-induced toxicity compared to pretreatments that protect against chemical injury. Cystamine treatment 12 hours after carbon tetrachloride (CCl₄) was reported to have therapeutic effects on CCl₄-induced hepatic necrosis via an unknown mechanism. The objectives of this project were to develop. quantitative animal models to characterize cystamine treatment of chemically-induced hepatotoxicity and to use the models to investigate possible mechanisms of the therapeutic effect. Cystamine produced dose related therapeutic effects against both CCl₄ and galactosamine-induced hepatic necrosis in male Sprague-Dawley rats. The therapeutic effect on galactosamine-induced damage demonstrated that cystamine has therapeutic effects that are unrelated to inhibition of early biochemical events initiating damage. This was an important finding since cystamine pretreatment will prevent CCl₄-induced hepatic damage by inhibiting the bioactivation of CCl₄. Cystamine-induced hypothermia did not cause a delay in the appearance of maximal hepatic damage. Cystamine also did not stimulate hepatic protein synthesis in intoxicated rats. Although cystamine was reduced to cysteamine in the livers of galactosamine treated rats the hepatic sulfhydryl content was only transiently affected by cystamine. Cystamine did not reduce toxicant-induced hepatic calcium accumulation, despite the fact that the influx of extracellular calcium into toxicant damaged cells is considered by many to be an irreversible event causing cell death. Cystamine also did not alter subcellular calcium distribution in toxicant treated rats or enhance recovery of microsomal calcium sequestration in CCl₄ treated rats. Since cystamine is metabolized to cysteamine in vivo and cysteamine can chelate calcium the effect of chelating agents and cysteamine analogs on galactosamine-induced hepatic damage was tested. Therapeutic effects were observed for the calcium chelators EDTA and EGTA, agents with a chelating structure similar to cysteamine (ie. a free amine and a free sulfhydryl on adjacent carbons), or agents which may be metabolized t0 such structures. The results suggest that calcium chelation may be a mechanism of therapeutic action in chemically-induced hepatotoxicity. A reduction of free calcium concentration via chelation would explain reduced cytotoxic consequences of toxicant-induced hepatic calcium accumulation.

Thesis (M.S.)--University of Michigan, 1970. / Typescript (photocopy). Includes bibliographical references (leaves 40-43). Also issued in print.