Graham, Valerie (2010)
M.Phil. thesis, University of Birmingham.
Thiopurine methyltransferase (TPMT) metabolises the widely prescribed thiopurine drugs. The activity of this enzyme varies between individuals and this can influence treatment success. Rapid and accurate assays of TPMT and 6TGN, the active thiopurine metabolites, are increasingly recognised as valuable clinical tools, to guide dosing and treatment. This work examines and develops methods for determining a patient's TPMT status and measuring 6TGN levels, adapting them for analysis using whole blood rather than washed red blood cell preparations. The advantages and limitations of these new assays in practice are investigated, which clearly shows that the more rapid new methods have increased clinical significance and utility. Experimental work and research provides an increased understanding of factors influencing determination and significance of a patient's TPMT status and thiopurine metabolite levels. This includes possible misclassification of TPMT status when expressing results in relation to patient haemoglobin and a longitudinal study of TPMT activity of patients commencing thiopurine therapy which demonstrates no enzyme induction.
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