Applications: Metabolomic assessment of the different Cytochrome P450 and UDP-Glucuronosyltransferase contributions to Warfarin Metabolism in individual patients
Every year two million people begin Coumadin therapy in the U.S. Coumadin (R-, S-Warfarin [War]) is a challenging drug to accurately dose, both initially and for maintenance, because of its narrow therapeutic range, wide inter-patient variability, and the long list of factors that can influence dosing. Recently, War was reported as the fourth leading cause of adverse drug events.
University researchers have disclosed the metabolic profile which encompasses both P450 and UDP Glucuronosyltransferase contributions to the turnover of warfarin and its metabolites. The discovery specifies the uses of liquid chromatography–tandem mass spectrometry (LC-MS/MS) analysis techniques to measure the warfarin metabolome and the variability of warfarin turn over which exist in different individuals. This disclosure specifies the use of different warfarin metabolites and derivatives for more precise control of coagulation times in different individuals.
These developments greatly improve both the treatment and the effective management of individual anticoagulant therapy strategies. This metabolic phenotyping and its uses are far superior to the use of genotyping which is predictive but does not address the variability that is recognized as a superior diagnostic. This strategy utilizes a metabolomic approach to develop a real time metabolic profile for a subject with regard to warfarin dosing. The profile may then be correlated with dose response, to provide better dosing efficacy and safety and/or may help identify superior derivative drug candidates.
Taken in total, this invention determines a patient's complete metabolic profile to establish the effective dose of a pharmaceutically active compound tailored specifically for an individual patient.
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