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Effect of CYP2C19 Genetic Polymorphism on Pharmacokinetics and Pharmacodynamics and Pharmacodynamics of a New Proton Pump Inhibitor, Ilaprazole
Author(s) -
Cho Hoon,
Choi MinKoo,
Cho DooYeon,
Yeo ChangWoo,
Jeong HyeEun,
Shon JiHong,
Lee JunYeoun,
Shin JaeSoo,
Cho Mong,
Kim DongYeon,
Shin JaeGook
Publication year - 2012
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270011408611
Subject(s) - cyp2c19 , pharmacodynamics , pharmacokinetics , pharmacology , proton pump inhibitor , metabolite , omeprazole , active metabolite , medicine , genotype , chemistry , metabolism , biochemistry , cytochrome p450 , gene
It is well known that the CYP2C19 genetic polymorphism influences the pharmacokinetics and pharmacodynamics of proton pump inhibitors (PPIs), but no report has addressed the effects on ilaprazole, a newly developed PPI. To investigate the effects of the CYP2C19 genetic polymorphism on the disposition and pharmacodynamics of ilaprazole, multiple doses of once‐daily 10 mg ilaprazole were repeatedly administered for 7 days to 27 healthy Korean participants, comprising 9 homozygous CYP2C19 extensive metabolizers (homo EMs), 10 heterozygous EMs (hetero EMs), and 8 homozygous poor metabolizers (PMs). The plasma concentration and pharmacodynamic response were measured in the last dose interval. Each genotype group was matched for gender and thus was composed of 4 male and 4 female participants when the analysis was conducted. The pharmacokinetic parameters estimated from the plasma concentrations of ilaprazole and its metabolite ilaprazole sulfone, the serum gastrin level, and the 24‐hour intragastric pH were compared among the CYP2C19 genotype groups. No statistically significant differences in the maximum plasma concentration at steady state(C ss, max ) and the area under the concentration‐time curve from zero to 24 hours (AUC τ ) of ilaprazole and ilaprazole sulfone were observed among the homo EM, hetero EM, and PM CYP2C19 genotypes. In addition, the mean 24‐hour intragastric pH, the percentage of time at pH>4, and the AUC τ of serum gastrin showed no significant differences among the CYP2C19 genotype groups. The data suggests that the pharmacokinetics and pharmacodynamics of ilaprazole are not significantly influenced by the CYP2C19 genetic polymorphism in healthy participants.