PK/PD modeling of rabeprazole in CYP2C19 genotypes: consideration of the influence of thio-ether metabolite, CYP3A4, accumulation and CYP2D6 polymorphism may help to better develop and validate the model.

摘要

The work of Sheng et al. is interesting in that an attempt is made to predict the PK/PD outcome of rabeprazole after a single-dose administration in healthy volunteers who have been appropriately genotyped [1]. As pointed out by the authors, the influence of genetic polymorphism on drug absorption per se has not been reported and therefore, the explanation of the differences observed in the clearance of rabeprazole has squarely rested on the influence of genetic polymorphism in CYP2C19 [1]. However, it does not factor in the influence of other variables that may have a tremendous impact on the end result of determining the overall influence of the CYP2C19 genotype on the PK/PD of rabeprazole in the relevant patient population at large.