Pharmacokinetics of the new proton pump inhibitor ilaprazole in Chinese healthy subjects in relation to CYP3A5 and CYP2C19 genotypes

Yalin Li, Wei Zhang, Dong Guo, Gan Zhou, Honghao Zhou, Zhousheng Xiao

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Background: PPIs are widely used in peptic diseases, and this paper is to investigate the kinetic characteristics of a new PPI ilaprazole in Chinese healthy subjects and the association with CYP3A5 and CYP2C19 polymorphisms. Methods: 21 subjects were selected and treated with 10mg ilaprazole according to their CYP3A5*3 genotypes (including 7 of CYP3A5*1/*1, 7 of *1/*3, and 7 of *3/*3). The plasma concentrations of ilaprazole and its metabolites were monitored by LC-MS/MS method. Results: The Cmax, AUC(0-6), AUC(0-48) and AUC(0-∞) of ilaprazole were all significantly different across the 3 CYP3A5 genotypes (including 4 of CYP3A5*1/*1, 4 of *1/*3, 3 of *3/*3; P < 0.05) in CYP2C19 wild-type subjects (CYP2C19 wt/wts), similar variety of Cmax and AUC(0-6) among CYP3A5 genotypes (including 3 of CYP3A5*1/*1, 3 of *1/*3, 4 of *3/*3; P < 0.05) were also observed in CYP2C19 heterozygous subjects (CYP2C19 wt/mts). The sulfoxidation metabolic index (measure of collective CYP3A activity) indicates that the CYP3A5*1/*1 (high-expressers), *1/*3 (low-expressers), and *3/*3 (no-expressers) groups have medium, lowest and highest activities on ilaprazole metabolism, inconsistent with genotype-based CYP3A5 enzymatic activity. Further analysis showed no correlation between ilaprazole metabolism and CYP2C19 genotypes, evidenced by that the AUC(0-∞) of ilaprazole from either CYP3A5*1/*1 or CYP3A5*1/*3 groups was much higher in CYP2C19 wt/wts (n = 4) than that in CYP2C19 wt/mts (n = 3) (P < 0.001), but the Cmax and AUC(0-6) of ilaprazole from CYP3A5*3/*3 groups, were significantly lower in CYP2C19 wt/wts (n = 3) compared to CYP2C19 wt/mts (n = 4) (P < 0.01). Conclusions: There was no demonstrated relationship between ilaprazole metabolism and CYP3A5 polymorphisms.

Original languageEnglish (US)
Pages (from-to)60-67
Number of pages8
JournalClinica Chimica Acta
Volume391
Issue number1-2
DOIs
StatePublished - May 1 2008

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Cytochrome P-450 CYP3A
Pharmacokinetics
Proton Pump Inhibitors
Healthy Volunteers
Genotype
Area Under Curve
Metabolism
ilaprazole
Cytochrome P-450 CYP2C19
Polymorphism
Metabolites

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

Pharmacokinetics of the new proton pump inhibitor ilaprazole in Chinese healthy subjects in relation to CYP3A5 and CYP2C19 genotypes. / Li, Yalin; Zhang, Wei; Guo, Dong; Zhou, Gan; Zhou, Honghao; Xiao, Zhousheng.

In: Clinica Chimica Acta, Vol. 391, No. 1-2, 01.05.2008, p. 60-67.

Research output: Contribution to journalArticle

@article{621e775c9b0a47faa76c0860cb84d869,
title = "Pharmacokinetics of the new proton pump inhibitor ilaprazole in Chinese healthy subjects in relation to CYP3A5 and CYP2C19 genotypes",
abstract = "Background: PPIs are widely used in peptic diseases, and this paper is to investigate the kinetic characteristics of a new PPI ilaprazole in Chinese healthy subjects and the association with CYP3A5 and CYP2C19 polymorphisms. Methods: 21 subjects were selected and treated with 10mg ilaprazole according to their CYP3A5*3 genotypes (including 7 of CYP3A5*1/*1, 7 of *1/*3, and 7 of *3/*3). The plasma concentrations of ilaprazole and its metabolites were monitored by LC-MS/MS method. Results: The Cmax, AUC(0-6), AUC(0-48) and AUC(0-∞) of ilaprazole were all significantly different across the 3 CYP3A5 genotypes (including 4 of CYP3A5*1/*1, 4 of *1/*3, 3 of *3/*3; P < 0.05) in CYP2C19 wild-type subjects (CYP2C19 wt/wts), similar variety of Cmax and AUC(0-6) among CYP3A5 genotypes (including 3 of CYP3A5*1/*1, 3 of *1/*3, 4 of *3/*3; P < 0.05) were also observed in CYP2C19 heterozygous subjects (CYP2C19 wt/mts). The sulfoxidation metabolic index (measure of collective CYP3A activity) indicates that the CYP3A5*1/*1 (high-expressers), *1/*3 (low-expressers), and *3/*3 (no-expressers) groups have medium, lowest and highest activities on ilaprazole metabolism, inconsistent with genotype-based CYP3A5 enzymatic activity. Further analysis showed no correlation between ilaprazole metabolism and CYP2C19 genotypes, evidenced by that the AUC(0-∞) of ilaprazole from either CYP3A5*1/*1 or CYP3A5*1/*3 groups was much higher in CYP2C19 wt/wts (n = 4) than that in CYP2C19 wt/mts (n = 3) (P < 0.001), but the Cmax and AUC(0-6) of ilaprazole from CYP3A5*3/*3 groups, were significantly lower in CYP2C19 wt/wts (n = 3) compared to CYP2C19 wt/mts (n = 4) (P < 0.01). Conclusions: There was no demonstrated relationship between ilaprazole metabolism and CYP3A5 polymorphisms.",
author = "Yalin Li and Wei Zhang and Dong Guo and Gan Zhou and Honghao Zhou and Zhousheng Xiao",
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TY - JOUR

T1 - Pharmacokinetics of the new proton pump inhibitor ilaprazole in Chinese healthy subjects in relation to CYP3A5 and CYP2C19 genotypes

AU - Li, Yalin

AU - Zhang, Wei

AU - Guo, Dong

AU - Zhou, Gan

AU - Zhou, Honghao

AU - Xiao, Zhousheng

PY - 2008/5/1

Y1 - 2008/5/1

N2 - Background: PPIs are widely used in peptic diseases, and this paper is to investigate the kinetic characteristics of a new PPI ilaprazole in Chinese healthy subjects and the association with CYP3A5 and CYP2C19 polymorphisms. Methods: 21 subjects were selected and treated with 10mg ilaprazole according to their CYP3A5*3 genotypes (including 7 of CYP3A5*1/*1, 7 of *1/*3, and 7 of *3/*3). The plasma concentrations of ilaprazole and its metabolites were monitored by LC-MS/MS method. Results: The Cmax, AUC(0-6), AUC(0-48) and AUC(0-∞) of ilaprazole were all significantly different across the 3 CYP3A5 genotypes (including 4 of CYP3A5*1/*1, 4 of *1/*3, 3 of *3/*3; P < 0.05) in CYP2C19 wild-type subjects (CYP2C19 wt/wts), similar variety of Cmax and AUC(0-6) among CYP3A5 genotypes (including 3 of CYP3A5*1/*1, 3 of *1/*3, 4 of *3/*3; P < 0.05) were also observed in CYP2C19 heterozygous subjects (CYP2C19 wt/mts). The sulfoxidation metabolic index (measure of collective CYP3A activity) indicates that the CYP3A5*1/*1 (high-expressers), *1/*3 (low-expressers), and *3/*3 (no-expressers) groups have medium, lowest and highest activities on ilaprazole metabolism, inconsistent with genotype-based CYP3A5 enzymatic activity. Further analysis showed no correlation between ilaprazole metabolism and CYP2C19 genotypes, evidenced by that the AUC(0-∞) of ilaprazole from either CYP3A5*1/*1 or CYP3A5*1/*3 groups was much higher in CYP2C19 wt/wts (n = 4) than that in CYP2C19 wt/mts (n = 3) (P < 0.001), but the Cmax and AUC(0-6) of ilaprazole from CYP3A5*3/*3 groups, were significantly lower in CYP2C19 wt/wts (n = 3) compared to CYP2C19 wt/mts (n = 4) (P < 0.01). Conclusions: There was no demonstrated relationship between ilaprazole metabolism and CYP3A5 polymorphisms.

AB - Background: PPIs are widely used in peptic diseases, and this paper is to investigate the kinetic characteristics of a new PPI ilaprazole in Chinese healthy subjects and the association with CYP3A5 and CYP2C19 polymorphisms. Methods: 21 subjects were selected and treated with 10mg ilaprazole according to their CYP3A5*3 genotypes (including 7 of CYP3A5*1/*1, 7 of *1/*3, and 7 of *3/*3). The plasma concentrations of ilaprazole and its metabolites were monitored by LC-MS/MS method. Results: The Cmax, AUC(0-6), AUC(0-48) and AUC(0-∞) of ilaprazole were all significantly different across the 3 CYP3A5 genotypes (including 4 of CYP3A5*1/*1, 4 of *1/*3, 3 of *3/*3; P < 0.05) in CYP2C19 wild-type subjects (CYP2C19 wt/wts), similar variety of Cmax and AUC(0-6) among CYP3A5 genotypes (including 3 of CYP3A5*1/*1, 3 of *1/*3, 4 of *3/*3; P < 0.05) were also observed in CYP2C19 heterozygous subjects (CYP2C19 wt/mts). The sulfoxidation metabolic index (measure of collective CYP3A activity) indicates that the CYP3A5*1/*1 (high-expressers), *1/*3 (low-expressers), and *3/*3 (no-expressers) groups have medium, lowest and highest activities on ilaprazole metabolism, inconsistent with genotype-based CYP3A5 enzymatic activity. Further analysis showed no correlation between ilaprazole metabolism and CYP2C19 genotypes, evidenced by that the AUC(0-∞) of ilaprazole from either CYP3A5*1/*1 or CYP3A5*1/*3 groups was much higher in CYP2C19 wt/wts (n = 4) than that in CYP2C19 wt/mts (n = 3) (P < 0.001), but the Cmax and AUC(0-6) of ilaprazole from CYP3A5*3/*3 groups, were significantly lower in CYP2C19 wt/wts (n = 3) compared to CYP2C19 wt/mts (n = 4) (P < 0.01). Conclusions: There was no demonstrated relationship between ilaprazole metabolism and CYP3A5 polymorphisms.

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U2 - 10.1016/j.cca.2008.02.003

DO - 10.1016/j.cca.2008.02.003

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VL - 391

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EP - 67

JO - Clinica Chimica Acta

JF - Clinica Chimica Acta

SN - 0009-8981

IS - 1-2

ER -