Abstract
Although the rat models described in the previous section elegantly emonstrate the efficacy of local immunosuppression, they have several limitations when one considers the potential for eventual clinical application. The osmotic pumps utilized for drug delivery are inaccessible within the abdomen, cannot be emptied of and refilled with drug, and can only infuse drug for a 2 week interval. As a result, long-term considerations such as pump compatibility, drug stability and catheterinduced thrombosis and infection cannot be evaluated. Furthermore, repeated blood sampling to assess regional and systemic pharmacokinetics is not practical. Despite the generalized species simililarity which exists in the pharmacokinetic advantage of regional drug delivery,1 the results obtained from these models may not be entirely relevant to higher animals and man in view of significant species differences in drug disposition and pharmacologic activity, a point well illustrated by the corticosteroids.2–6 Finally, heterotopic placement of the transplanted organ to increase the pharmacokinetic advantage achievable from local infusion of a particular drug is not clinically feasible.
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Gruber, S.A., Xiao, S., Hughes, S.E. (1996). Local Heparin, 6-Mercaptopurine, Prednisolone, and Mizoribine Delivery in a Canine Renal Allograft Model. In: Local Immunosuppression of Organ Transplants. Medical Intelligence Unit. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-22105-1_9
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DOI: https://doi.org/10.1007/978-3-662-22105-1_9
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