Abstract: The invention provides methods for predicting toxicity related to calcineurin inhibition therapy by measuring the peak concentration of drug and the trough concentration of the drug, calculating a peak-trough fluctuation, and comparing this peak-trough fluctuation to known values to predict if the patient will exhibit calcineurin-inhibition therapy-related toxicity. The invention also provides methods for monitoring drug levels to ensure that a patient receiving calcineurin inhibition therapy remains within a therapeutic window which maximizes the efficacy and minimizes the toxicity of the calcineurin inhibitor. The invention also provides dosage methods which maximize the peak concentration, minimize the trough concentration, and maximize the fluctuation between peak and trough concentration of calcineurin inhibitors, to maximize the efficacy of the calcineurin inhibition therapy, and minimize the risk of developing calcineurin-inhibition therapy-related toxicity.

Abstract: The synthesis of deuterated analogues of rapamycin is disclosed together with a method for use for inducing immunosupression and in the treatment of transplantation rejection, graft vs host disease, autoimmune diseases, diseases of inflammation leukemia/lymphoma, solid tumors, fungal infections, hyperproliferative vascular disorders. Also described is a method for the synthesis of water soluble deuteratred rapamycin compounds and their use as described above.

Abstract: Deuterated rapamycin can be controllably introduced target locations within the patient's body by using an implantable medical device having a structure incorporated with a therapeutic agent comprising a deuterated rapamycin. Representative deuterated rapamycins include epi-7-deuteromthyl rapamycin, 7,43-d6 rapamycin, 7-deuteromethyl rapamycin and 31,42-d2-rapamycin and isomers thereof, and mixtures thereof. The deuterated rapamycin can also be glycosylated.

Abstract: The synthesis of deuterated analogues of rapamycin is disclosed together with a method for use for inducing immunosupression and in the treatment of transplantation rejection, graft vs host disease, autoimmune diseases, diseases of inflammation leukemia/lymphoma, solid tumors, fungal infections, hyperproliferative vascular disorders. Also described is a method for the synthesis of water soluble deuteratred rapamycin compounds and their use as described above.