Ph.d. / Bilag i særskilt bind.

Thesis (Ph. D.)--University of Texas at Austin, 2002. / Vita. Includes bibliographical references. Available also from UMI Company.

Cyclosporine (CsA) is commercially available for oral administration as a solution in olive oil with alcohol and an emulsifier. This formulation suffers from the disadvantages of poor and highly variable absorption, objectionable taste and difficulty in measuring the prescribed dose by visually impaired patients. Several oral formulations were prepared and tested in vitro and in vivo in dogs. Based on these preliminary results the dosage form chosen for evaluation was a tablet formulation prepared by direct compression. These tablets were compared to the commercial oil solution placed into soft gelatin capsules. In order to determine absolute bioavailability and to avoid the concern of time-dependent clearance, an intravenous tracer dose of ³H-CsA was simultaneously administered with each oral test product on each of two occasions. Absolute bioavailability was 46.0 ± 11.1% and 45.4 ± 9.9% for the capsules and tablets, respectively. C(max), t(max) and MRT were not significantly different between the two products. No differences were observed in the pharmacokinetics of the intravenously administered CsA in the two experiments which were separated by 8-13 days. The elderly, usually defined as people over 65 years of age, constitute about 12% of the U.S. population. It has been estimated that one out of four elderly people is arthritic and is, therefore, a candidate for chronic salicylate therapy. The pharmacokinetics of salicylate following a single oral solution dose of 600 mg of sodium salicylate were investigated in 22 healthy, nonsmoking male subjects. The plasma concentration and urinary excretion of salicylic acid and its metabolite, salicyluric acid, as well as the urinary excretion of salicyl glucuronides were monitored. Urinary recovery essentially accounted for the administered dose and was not influenced by age, nor was the apparent oral clearance of salicylic acid. Assuming no presystemic elimination, it could be concluded that systemic availability is unaffected by age. An increase in the apparent volume of distribution, V(area), and a decrease in the maximum plasma salicylic acid concentration with age were observed. Renal clearance of salicyluric acid decreased significantly with age and was found to correlate significantly with creatinine clearance.

Thesis (Ph. D.)--University of Texas at Austin, 2002. / Vita. Includes bibliographical references. Available also from UMI Company.

Not available / text

Cyclosporine A (CsA) is a widely used immunosuppressive drug which has novel, clinically beneficial effects on the immune system. Substantial evidence indicates that CsA acts preferentially by impairing T cell lymphokine production, but there is some evidence that CsA may also affect B cells and other antigen presenting cells directly. Using an in vitro antibody response to sheep red blood cells, we have examined the effect CsA has on different populations of mouse lymphocytes. CsA appears to have a direct inhibitory effect on highly purified B cells from naive animals in a dose dependent manner at physiologically achievable levels in vitro. Even antigen stimulated B cells were found to be sensitive to the late addition of CsA when the drug was added simultaneously with lymphokine. B cells and T cells briefly pulsed with CsA do not recover to produce antibody when CsA is removed. Indeed, B cells from naive animals treated in vivo with CsA and stimulated in vitro with lymphokine and SRBC to produce antibody are profoundly inhibited from producing PFC despite the absence of CsA in culture. These findings suggest that CsA has direct irreversible, fast acting inhibitory effects on B lymphocytes aside from or in addition to its effects on T cells. / Department of Biology

Univ., Diss.--Jena, 2001.

Thesis (doctoral)--Lunds Universitet, Malmö, 1993. / Added t.p. with thesis statement inserted. Includes bibliographical references.

Thesis (doctoral)--Lund University, 1997. / Added t.p. with thesis statement inserted.

Thesis (doctoral)--Lunds Universitet, Malmö, 1993. / Added t.p. with thesis statement inserted. Includes bibliographical references.