Why the study?
Are the activities of multiple CYPs associated with warfarin metabolism correlated with each other?
Are the activities of multiple CYPs associated with warfarin metabolism correlated with each other?
The enantio- and regio-selective metabolisms of warfarin are correlated, suggesting that CYP2C9, CYP1A2, and CYP3A4 may be regulated by common transcriptional mechanisms.
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Correlations suggest coordinated CYP regulation in warfarin metabolism; hypothesis-generating and should not yet inform dosing.
AIM: To clarify whether the activities of multiple CYPs associated with warfarin metabolism would be correlated with each other. METHODS: Oral clearances (CLpo) of warfarin enantiomers were estimated in 378 Chinese, Caucasians and African-Americans. The partial metabolic clearances (CLm) for 7-hydroxywarfarin enantiomers were also measured. In addition, CLpo and CLm were determined in a patient on warfarin and rifampicin. RESULTS: Correlations between CLpo for warfarin enantiomers existed across the three populations. In addition, there was a significant correlation between the CLm for 7-hydroxylation of warfarin enantiomers. Under induced conditions by rifampicin, there were significant correlations between the enantio- and regio-selective metabolisms of warfarin. CONCLUSION: Metabolic activities of CYP2C9, CYP1A2 and CYP3A4 may be regulated by common transcriptional mechanism(s).
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Takahashi et al. (2016) studied this question.
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