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Pharmacokinetics of cyclosporine A in normal and carrier dogs for Alport Syndrome and transdermal absorption of cyclosporine A in normal dogs
Cyclosporine A is a fungal 11 amino acid cyclic polypeptide characterized by potent immunosuppressive activity. CsA selectively inhibits T lymphocytes, without any direct effect on B lymphocytes. Allograft and patient survival rates for all solid organ transplant recipients have improved significantly since CsA was introduced for clinical use. CsA is also effective in the treatment of autoimmune diseases. After oral administration, CsA is extensively metabolized by the cytochrome P-450IIIA enzyme systems in the small intestines and the liver and then excreted in the bile. Oral bioavailability of CsA is markedly variable among patients, necessitating drug monitoring. CsA has a narrow therapeutic window, whereas low concentrations are ineffective, slightly high concentrations can be nephrotoxic or hepatotoxic. The pharmacokinetics of CsA changes in some disease states due to alterations in blood binding properties of CsA. One objective of this study was to determine the pharmacokinetics of CsA in apparently healthy normal dogs and in carrier dogs for Alport syndrome, and to compare the pharmacokinetics of CsA between the two groups after single oral administration. There were no differences in CsA pharmacokinetics between apparently normal dogs and carrier female dogs for Alport syndrome. Hematocrit, serum cholesterol and plasma protein concentrations in dogs with Alport syndrome were within normal ranges, which was consistent with the finding that CsA pharmacokinetics were unchanged. Topical administration of CsA in dermatologic disorders may be more convenient than oral administration. Its large molecular weight, ring structure, and high lipophilicity make its transdermal absorption difficult. The objectives of this study were; 1) to determine availability of transdermal CsA when applied topically in pleuronic lecithine gel (PLO); 2) to determine the dose and formulation of CsA in the transdermal gel system necessary to achieve therapeutic concentrations; 3) to determine the relative (compared with oral) bioavailability of CsA PLO gel in dogs. In this study CsA PLO gel failed to provide transdermal absorption of CsA.
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Includes bibliographical references (leaves 58-66).
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Inan, Guvenc (2002). Pharmacokinetics of cyclosporine A in normal and carrier dogs for Alport Syndrome and transdermal absorption of cyclosporine A in normal dogs. Master's thesis, Texas A&M University. Available electronically from
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