Cytochrome P450 oxidoreductase genetic polymorphism and pantoprazole pharmacokinetics in healthy volunteers

Mateusz Kurzawski, Barbara Gawrońska-Szklarz, Urszula Adamiak-Giera, Elżbieta Wyska, Marek Droździk, Sylwia Szeląg-Pieniek



Introduction: It has recently been demonstrated that CYP2C19 activity may be influenced not only by CYP2C19 polymorphism, but also cytochrome P450 oxidoreductase (POR) protein abundance in human liver microsomes. The human POR gene is highly polymorphic and a common POR*28 allele is associated with increased POR activity, which may result in increased CYP P450 activity (including CYP2C19).

The aim of the current study was to evaluate the association between POR and CYP2C19 polymorphisms and CYP2C19 substrate pharmacokinetics, i.e. pantoprazole, in Polish Caucasian healthy volunteers.

Materials and methods: The study enrolled 30 subjects, genotyped for rs4244285 (681G>A, CYP2C19*2), rs12248560 (−806C>T, CYP2C19*17) and rs1057868 (31696C>T, POR*28). Pantoprazole concentration in plasma was determined by validated high-performance liquid-chromatography method 1 h, 2 h, 3 h, 4 h, 6 h and 8 h after a single oral 40 mg dose of the drug.

Results: No significant differences in the drug concentrations between POR*1/*1, POR*1/*28 and POR*28/*28 carriers were observed. Multivariate analysis revealed that the CYP2C19 genotype significantly influenced all the investigated pharmacokinetic parameters (p < 0.05), while the POR genotype was not associated with any of the parameters.

Conclusions: The results of the current study suggest that POR polymorphism does not significantly influence pantoprazole pharmacokinetics.


pantoprazole; pharmacokinetics; pharmacogene­tics; POR; cytochrome P450 oxidoreductase

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