Bioavailability and activity of prednisone and prednisolone in the feline patient

Abstract

In veterinary dermatology, the therapeutic approach to numerous diseases (e.g. hypersensitivity and autoimmunity) centres upon suppression of an overactive immune system. By contrast, in other situations such as infectious diseases and cancer, it may be desirable to enhance an ineffective immune response. Currently available methods of such immunomodulation are relatively crude. Immunosuppression is generally achieved with systemic administration of glucocorticoids, with or without concurrent cytotoxic agents. These drugs affect the function of a wide range of immune cells and produce a blanket immunosuppression that not only inhibits the desired immune response, but may also nonspecifically inhibit protective responses to potential pathogens. Even more refined agents, such as cyclosporin A, have broad immunosuppressive effects on T lymphocytes of a wide range of antigenic specificity. Similarly, current immunomodulatory drugs (e.g. levamisole and bacterial derivatives) are relatively crude agents with poorly characterised modes of action and poor clinical efficacies.There are some exceptions amongst the current broad-spectrum approach to immunomodulation, including hyposensitization therapy for atopic dermatitis, autogenous vaccination for staphylococcal pyoderma, and the use of intravenous gammaglobulin therapy for immune-mediated skin disease. These procedures may be clinically effective, but the mechanisms of their effects are not fully understood. The use of recombinant cytokine therapy (e.g. omega interferon) is a further example of the beginnings of the use of more targeted immunotherapy in veterinary medicine. Future approaches to the treatment of numerous diseases will involve novel immunomodulatory agents. Such therapies derive from rapid progress in understanding basic immunological mechanisms, particularly the concept that most immune responses are regulated by cytokines released by specific populations of T lymphocytes: Th1, Th2, Th3 and Treg. Currently, much attention focuses on the cytokine IL-10, which has a key role in the suppression of autoimmune and allergic responses. With this knowledge, therapies aimed at manipulating the cytokine milieu, or inducing a particular cytokine profile at the time of antigen exposure, are under investigation. There are various approaches to achieving this aim, including: (1) administration of recombinant cytokines; (2) administration of monoclonal antibodies that can neutralise specific cytokines or block other immunological processes; and (3) administration of genes encoding cytokines via carrier microbes or naked DNA therapy that may be enhanced by the use of molecular adjuvants. Other novel therapeutic approaches focus on the delivery of antigens, small peptides derived from such antigens, or genes encoding antigens delivered via novel routes, including percutaneous, intranasal and oral. Depending upon the protocol, use of these delivery routes can stimulate potent mucosal immune responses, often using mucosal adjuvants, or alternatively, induce systemic tole...

Plasma and Ocular Prednisolone Disposition after Oral Treatment in Cats

“…While higher systemic exposure of prednisolone was previously reported in cats [13], the rate of drug absorption and elimination was comparable to our present results. A feasible explanation for the different results could be attributed to differences in animal weight and, thus, in volume of distribution.…”

“…In the present study, we reported plasma half-life time of elimination of 0.66 h, comparable to previous reports in cats [13]. On the contrary, longer T 1/2el values (around 3 h) were reported after oral prednisolone in humans [6, 29].…”

“…Previous studies on plasma pharmacokinetics of prednisolone have been performed in humans, rats, rabbits, cows, sheep, horses, dogs, and cats [6–13], but there are no reports about ocular disposition of the corticoid after oral administration in any of those species. In order to characterize the pharmacokinetics of prednisolone in different biological matrices, an analytical technique needs to be developed to obtain precise and accurate results.…”

Glucocorticoid Therapy

“…It is not clear if the differences are due to decreased gastrointestinal absorption or to decreased hepatic conversion of prednisone to prednisolone (Graham-Mize and Rosser, 2004). However, this belief does not seem to be correct.…”

Feline Atopic Dermatitis: A Retrospective Study of 194 Cases (1988^|^ndash;2003)

“…The majority of these cats received long-term systemic glucocorticoids. Some cats cannot convert the prodrug prednisone to the active drug prednisolone 11) , so prednisolone is the preferred form in cats 26) . In our study, only 56.3% of the cats responded to prednisone, while 83.7% responded to prednisolone.…”