Besides the activity, the metabolic profiles of the 2 enantiomers have also been found to differ. Warfarin exerts its anti-coagulant effect by non-competitively inhibiting the action of vitamin K epoxide reductase complex subunit 1 in an allosteric manner. VKORC1 catalyses the conversion of vitamin K epoxide to reduced vitamin K, an essential co-factor for c-glutamylcarboxylase. GGCX is an enzyme which catalyses the c-carboxylation of glutamic acid residues of clotting factors and proteins C, S and Z. Lately, functional genetic variants in the VKORC1 gene have been found to affect the pharmacodynamics of warfarin and influence its dosage requirements in patients. Rieder et al., have previously identified five haplotypes which are differentiated by five non-coding single nucleotide polymorphisms. These five haplotypes were found to segregate the patients into low- and high- dose groups and account for approximately 25% of the variability in warfarin doses. In a more recent study in Asian population, the VKORC1 diplotypes were found to contribute to approximately 59.1% of the variability in warfarin dose requirement. In multivariate analysis, age, weight and genetic polymorphisms presenting CYP2C9 and VKORC1 accounted for 74.2% of the warfarin dose variability. Approximately 25% of the variations in dose requirements still remained unexplained. Although the availability of high-throughput genotyping capabilities can facilitate pharmacodynamics-based pharmacogenetic studies, pharmacoproteomic studies may provide additional information regarding variability in warfarin dose requirements in patients. Phenotypic traits are often the result of various proteins functioning in a concerted manner post-translationally and may be important in influencing interindividual variations to warfarin treatment. The field of pharmacoproteomics may be more important than the pharmacogenetics of individual patients as it represents the effects of post-translational modifications of functional proteins which are responsible for the phenotypic effects and may serve as important biomarkers in patients. The objective of this exploratory study was to investigate the proteomic profile of patients receiving low- and high-dose warfarin and to perform correlative studies between genotypic and proteomic markers in the two groups of patients. The field of pharmacoproteomics is fast expanding and is proving to be a useful SP600125 adjunct to pharmacogenetics and pharmacogenomics in drug development, diagnostics, drug safety and toxicology studies. In addition to pharmacogenetic factors, pharmacoproteomic profiling in patients has several associated advantages with regards to personalized drug therapy: firstly, it is directly associated with the observed phenotypic changes following drug therapy and secondly.