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Title: Therapeutic drug monitoring of novel immunosuppressants
Author: Cattaneo, Dario.
Awarding Body: Open University
Current Institution: Open University
Date of Award: 2006
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Therapeutic drug monitoring is primarily undertaken for narrow therapeutic inde:drugs, such as immunosuppressants. These drugs have reduced the incidence of acute rejection and improved allograft survival. However, due to their narrow therapeutic index, small variations in blood levels may result in inadequate levels of immunosuppression or toxic drug concentrations. To overcome these problems individual dose regimen based-on phannacokinetic monitoring has been proposed in the past years. Indeed, several studies have previously documented a significant association between cyclosporine whole blood levels and patient's clinical outcome, expressed as rejection episodes as well as drug-related adverse events. Novel immunosuppressive agents have been recently introduced on the market (such as rapamycins and mycophenolic acid-releasing formulations). However, data on their phannacokinetics, which in tum could be useful for the definition of therapeutic ranges, are scanty. To address this issue we have used a chromatographic method for the measurement of mycophenolic acid levels in kidney transplant recipients. Although this immunosuppressant is usually given in a fixed daily dose regimen, we found a positive correlation between drug levels, but not dose, and renal function. As additional analysis, significant phannacokinetic interactions between mycophenolic acid and concomitant immunosuppressive regimens have been identified. Similarly, novel chromatographic methods for the analysis of rapamycins in the whole blood have been developed in our laboratory, and applied to identify phannacokinetic interactions between these anJ other inununosuppressive agents. In the last part of my research project. I have also presented preliminary data on the application of pharmacogenetics analysis in patients given cyclosporine as part of their immunosuppressive regimenIn conclusion, it can be reasonably speculated that TDM based on pharmacokinetic. as well as novel pharmacogenetic approaches, can be considered as reliable tools to guide drug dosing in organ transplantation setting, ultimately resulting in a significant improvement of long term graft and patient survival
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available