Application of in vitro-in vivo extrapolation (IVIVE) and physiologically based pharmacokinetic (PBPK) modelling to investigate the impact of the CYP2C8 polymorphism on rosiglitazone exposure.

Abstract excerpt

PURPOSE: To predict the impact of the CYP2C8 3 genotype on rosiglitazone exposure in the absence and presence of trimethoprim. METHODS: Prior in vitro and in vivo information for rosiglitazone and trimethoprim were collated from the literature. Specifically, data on the frequency of the different allelic forms of CYP2C8 and their metabolic activity for rosiglitazone were incorporated into a physiologically-based...

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