Gender, but Not CYP2C19 Genotypes and CYP3A Phenotypes, is a Major Determinant of Ilaprazole Pharmacokinetic

Shan Cao; Gan Zhou; Yao Chen; Dong Guo; Zhi-rong Tan; Lan Fan; Hai-tang Hu; Xiang-hong Qin; Hong-hao Zhou; Dong-sheng Ouyang; Wei Zhang

doi:doi:10.11648/j.ajls.s.2015030104.13

Gender, but Not CYP2C19 Genotypes and CYP3A Phenotypes, is a Major Determinant of Ilaprazole Pharmacokinetic

Shan Cao, Gan Zhou, Yao Chen, Dong Guo, Zhi-rong Tan, Lan Fan, Hai-tang Hu, Xiang-hong Qin, Hong-hao Zhou, Dong-sheng Ouyang, Wei Zhang

Published in American Journal of Life Sciences (Volume 3, Issue 1-4)

Received: 16 September 2014 Accepted: 24 November 2014 Published: 27 January 2015

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Abstract

The purpose of the study was to assess the impact of CYP2C19 genotypes, CYP3A phenotypes and gender-related difference on the pharmacokinetics of new proton pump inhibitor ilaprazole. Twenty-four healthy Chinese volunteers (age 24.0  1.9 years) were enrolled in an open-label study stratified for gender (12 males and 12 females) and their CYP2C19 genotype (12 of CYP2C19*1/*1 and 12 of CYP2C19*1/*2 or *1/*3). After a single 10-mg dose of ilaprazole was administrated, blood samples were collected at time 0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36h from all subjects. Ilaprazole and its metabolite sulfone-ilaprazole plasma concentrations were measured using the well-validated HPLC/MS/MS method. CYP3A phenotype was determined by the classic CYP3A probe drug midazolam one week after the clinical trial. The kinetics characteristics of ilaprazole and sulfone-ilaprazole were significantly influenced by gender. The clearance/systemic bioavailability (CL/F) of ilaprazole was much lower in female than in male (2.5  1.0 versus 3.7  1.6 h-1, P = 0.029), difference became more significant even after corrected by body weight (P = 0.008). However, the differences on half-life, AUC0-36 and AUC0→∞ of ilaprazole between genders were not significantly after normalized by body weight. As for sulfone ilaprazole, larger AUC0→36 and AUC0→∞ were detected in female when compared with male (406.8  126.3 vs. 246.7  70.0 ng • h/ml, P = 0.007, and 606.7  224.5 vs. 332.0  117.1 ng • h/ml, P = 0.001), discrepancies were still significant after corrected by total body weight, P value were 0.017 and 0.010 respectively. The pharmacokinetics parameters of ilaprazole and ilaprazole sulfone were neither different across CYP2C19 genotype groups nor related to CYP3A phenotype. CL/F of ilaprazole were much smaller in women than in men even after adjusted by body weight, indicating great effect of gender on the pharmacokinetics of ilaprazole. CYP2C19 genotypes and CYP3A phenotypes did not affect the pharmacokinetics of ilaprazole or sulfone-ilaprazole.

Published in	American Journal of Life Sciences (Volume 3, Issue 1-4) This article belongs to the Special Issue Pharmacogenomics & Personalized Medicine
DOI	10.11648/j.ajls.s.2015030104.13
Page(s)	14-20
Creative Commons	This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.
Copyright	Copyright © The Author(s), 2015. Published by Science Publishing Group

Keywords

CYP2C19, CYP3A Phenotype, Ilaprazole, Pharmacokinetics, Gender Difference

References

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APA Style

Shan Cao, Gan Zhou, Yao Chen, Dong Guo, Zhi-rong Tan, et al. (2015). Gender, but Not CYP2C19 Genotypes and CYP3A Phenotypes, is a Major Determinant of Ilaprazole Pharmacokinetic. American Journal of Life Sciences, 3(1-4), 14-20. https://doi.org/10.11648/j.ajls.s.2015030104.13

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ACS Style

Shan Cao; Gan Zhou; Yao Chen; Dong Guo; Zhi-rong Tan, et al. Gender, but Not CYP2C19 Genotypes and CYP3A Phenotypes, is a Major Determinant of Ilaprazole Pharmacokinetic. Am. J. Life Sci. 2015, 3(1-4), 14-20. doi: 10.11648/j.ajls.s.2015030104.13

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AMA Style

Shan Cao, Gan Zhou, Yao Chen, Dong Guo, Zhi-rong Tan, et al. Gender, but Not CYP2C19 Genotypes and CYP3A Phenotypes, is a Major Determinant of Ilaprazole Pharmacokinetic. Am J Life Sci. 2015;3(1-4):14-20. doi: 10.11648/j.ajls.s.2015030104.13

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@article{10.11648/j.ajls.s.2015030104.13,
  author = {Shan Cao and Gan Zhou and Yao Chen and Dong Guo and Zhi-rong Tan and Lan Fan and Hai-tang Hu and Xiang-hong Qin and Hong-hao Zhou and Dong-sheng Ouyang and Wei Zhang},
  title = {Gender, but Not CYP2C19 Genotypes and CYP3A Phenotypes, is a Major Determinant of Ilaprazole Pharmacokinetic},
  journal = {American Journal of Life Sciences},
  volume = {3},
  number = {1-4},
  pages = {14-20},
  doi = {10.11648/j.ajls.s.2015030104.13},
  url = {https://doi.org/10.11648/j.ajls.s.2015030104.13},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ajls.s.2015030104.13},
  abstract = {The purpose of the study was to assess the impact of CYP2C19 genotypes, CYP3A phenotypes and gender-related difference on the pharmacokinetics of new proton pump inhibitor ilaprazole. Twenty-four healthy Chinese volunteers (age 24.0  1.9 years) were enrolled in an open-label study stratified for gender (12 males and 12 females) and their CYP2C19 genotype (12 of CYP2C19*1/*1 and 12 of CYP2C19*1/*2 or *1/*3). After a single 10-mg dose of ilaprazole was administrated, blood samples were collected at time 0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36h from all subjects. Ilaprazole and its metabolite sulfone-ilaprazole plasma concentrations were measured using the well-validated HPLC/MS/MS method. CYP3A phenotype was determined by the classic CYP3A probe drug midazolam one week after the clinical trial. The kinetics characteristics of ilaprazole and sulfone-ilaprazole were significantly influenced by gender. The clearance/systemic bioavailability (CL/F) of ilaprazole was much lower in female than in male (2.5  1.0 versus 3.7  1.6 h-1, P = 0.029), difference became more significant even after corrected by body weight (P = 0.008). However, the differences on half-life, AUC0-36 and AUC0→∞ of ilaprazole between genders were not significantly after normalized by body weight. As for sulfone ilaprazole, larger AUC0→36 and AUC0→∞ were detected in female when compared with male (406.8  126.3 vs. 246.7  70.0 ng • h/ml, P = 0.007, and 606.7  224.5 vs. 332.0  117.1 ng • h/ml, P = 0.001), discrepancies were still significant after corrected by total body weight, P value were 0.017 and 0.010 respectively. The pharmacokinetics parameters of ilaprazole and ilaprazole sulfone were neither different across CYP2C19 genotype groups nor related to CYP3A phenotype. CL/F of ilaprazole were much smaller in women than in men even after adjusted by body weight, indicating great effect of gender on the pharmacokinetics of ilaprazole. CYP2C19 genotypes and CYP3A phenotypes did not affect the pharmacokinetics of ilaprazole or sulfone-ilaprazole.},
 year = {2015}
}

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TY  - JOUR
T1  - Gender, but Not CYP2C19 Genotypes and CYP3A Phenotypes, is a Major Determinant of Ilaprazole Pharmacokinetic
AU  - Shan Cao
AU  - Gan Zhou
AU  - Yao Chen
AU  - Dong Guo
AU  - Zhi-rong Tan
AU  - Lan Fan
AU  - Hai-tang Hu
AU  - Xiang-hong Qin
AU  - Hong-hao Zhou
AU  - Dong-sheng Ouyang
AU  - Wei Zhang
Y1  - 2015/01/27
PY  - 2015
N1  - https://doi.org/10.11648/j.ajls.s.2015030104.13
DO  - 10.11648/j.ajls.s.2015030104.13
T2  - American Journal of Life Sciences
JF  - American Journal of Life Sciences
JO  - American Journal of Life Sciences
SP  - 14
EP  - 20
PB  - Science Publishing Group
SN  - 2328-5737
UR  - https://doi.org/10.11648/j.ajls.s.2015030104.13
AB  - The purpose of the study was to assess the impact of CYP2C19 genotypes, CYP3A phenotypes and gender-related difference on the pharmacokinetics of new proton pump inhibitor ilaprazole. Twenty-four healthy Chinese volunteers (age 24.0  1.9 years) were enrolled in an open-label study stratified for gender (12 males and 12 females) and their CYP2C19 genotype (12 of CYP2C19*1/*1 and 12 of CYP2C19*1/*2 or *1/*3). After a single 10-mg dose of ilaprazole was administrated, blood samples were collected at time 0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36h from all subjects. Ilaprazole and its metabolite sulfone-ilaprazole plasma concentrations were measured using the well-validated HPLC/MS/MS method. CYP3A phenotype was determined by the classic CYP3A probe drug midazolam one week after the clinical trial. The kinetics characteristics of ilaprazole and sulfone-ilaprazole were significantly influenced by gender. The clearance/systemic bioavailability (CL/F) of ilaprazole was much lower in female than in male (2.5  1.0 versus 3.7  1.6 h-1, P = 0.029), difference became more significant even after corrected by body weight (P = 0.008). However, the differences on half-life, AUC0-36 and AUC0→∞ of ilaprazole between genders were not significantly after normalized by body weight. As for sulfone ilaprazole, larger AUC0→36 and AUC0→∞ were detected in female when compared with male (406.8  126.3 vs. 246.7  70.0 ng • h/ml, P = 0.007, and 606.7  224.5 vs. 332.0  117.1 ng • h/ml, P = 0.001), discrepancies were still significant after corrected by total body weight, P value were 0.017 and 0.010 respectively. The pharmacokinetics parameters of ilaprazole and ilaprazole sulfone were neither different across CYP2C19 genotype groups nor related to CYP3A phenotype. CL/F of ilaprazole were much smaller in women than in men even after adjusted by body weight, indicating great effect of gender on the pharmacokinetics of ilaprazole. CYP2C19 genotypes and CYP3A phenotypes did not affect the pharmacokinetics of ilaprazole or sulfone-ilaprazole.
VL  - 3
IS  - 1-4
ER  -

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Author Information

Shan Cao

Department of Clinical Pharmacology, Xingya Hospital, Central South University, Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha, Hunan, China
Gan Zhou

Department of Clinical Pharmacology, Xingya Hospital, Central South University, Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha, Hunan, China
Yao Chen

Department of Clinical Pharmacology, Xingya Hospital, Central South University, Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha, Hunan, China
Dong Guo

Department of Clinical Pharmacology, Xingya Hospital, Central South University, Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha, Hunan, China
Zhi-rong Tan

Department of Clinical Pharmacology, Xingya Hospital, Central South University, Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha, Hunan, China
Lan Fan

Department of Clinical Pharmacology, Xingya Hospital, Central South University, Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha, Hunan, China
Hai-tang Hu

Liyzon Pharmaceutical Group Inc., Guihua Road North, Zhuhai, China
Xiang-hong Qin

Liyzon Pharmaceutical Group Inc., Guihua Road North, Zhuhai, China
Hong-hao Zhou

Department of Clinical Pharmacology, Xingya Hospital, Central South University, Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha, Hunan, China
Dong-sheng Ouyang

Department of Clinical Pharmacology, Xingya Hospital, Central South University, Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha, Hunan, China
Wei Zhang

Department of Clinical Pharmacology, Xingya Hospital, Central South University, Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha, Hunan, China

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APA Style

Shan Cao, Gan Zhou, Yao Chen, Dong Guo, Zhi-rong Tan, et al. (2015). Gender, but Not CYP2C19 Genotypes and CYP3A Phenotypes, is a Major Determinant of Ilaprazole Pharmacokinetic. American Journal of Life Sciences, 3(1-4), 14-20. https://doi.org/10.11648/j.ajls.s.2015030104.13

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ACS Style

Shan Cao; Gan Zhou; Yao Chen; Dong Guo; Zhi-rong Tan, et al. Gender, but Not CYP2C19 Genotypes and CYP3A Phenotypes, is a Major Determinant of Ilaprazole Pharmacokinetic. Am. J. Life Sci. 2015, 3(1-4), 14-20. doi: 10.11648/j.ajls.s.2015030104.13

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AMA Style

Shan Cao, Gan Zhou, Yao Chen, Dong Guo, Zhi-rong Tan, et al. Gender, but Not CYP2C19 Genotypes and CYP3A Phenotypes, is a Major Determinant of Ilaprazole Pharmacokinetic. Am J Life Sci. 2015;3(1-4):14-20. doi: 10.11648/j.ajls.s.2015030104.13

Copy | Download

@article{10.11648/j.ajls.s.2015030104.13,
  author = {Shan Cao and Gan Zhou and Yao Chen and Dong Guo and Zhi-rong Tan and Lan Fan and Hai-tang Hu and Xiang-hong Qin and Hong-hao Zhou and Dong-sheng Ouyang and Wei Zhang},
  title = {Gender, but Not CYP2C19 Genotypes and CYP3A Phenotypes, is a Major Determinant of Ilaprazole Pharmacokinetic},
  journal = {American Journal of Life Sciences},
  volume = {3},
  number = {1-4},
  pages = {14-20},
  doi = {10.11648/j.ajls.s.2015030104.13},
  url = {https://doi.org/10.11648/j.ajls.s.2015030104.13},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ajls.s.2015030104.13},
  abstract = {The purpose of the study was to assess the impact of CYP2C19 genotypes, CYP3A phenotypes and gender-related difference on the pharmacokinetics of new proton pump inhibitor ilaprazole. Twenty-four healthy Chinese volunteers (age 24.0  1.9 years) were enrolled in an open-label study stratified for gender (12 males and 12 females) and their CYP2C19 genotype (12 of CYP2C19*1/*1 and 12 of CYP2C19*1/*2 or *1/*3). After a single 10-mg dose of ilaprazole was administrated, blood samples were collected at time 0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36h from all subjects. Ilaprazole and its metabolite sulfone-ilaprazole plasma concentrations were measured using the well-validated HPLC/MS/MS method. CYP3A phenotype was determined by the classic CYP3A probe drug midazolam one week after the clinical trial. The kinetics characteristics of ilaprazole and sulfone-ilaprazole were significantly influenced by gender. The clearance/systemic bioavailability (CL/F) of ilaprazole was much lower in female than in male (2.5  1.0 versus 3.7  1.6 h-1, P = 0.029), difference became more significant even after corrected by body weight (P = 0.008). However, the differences on half-life, AUC0-36 and AUC0→∞ of ilaprazole between genders were not significantly after normalized by body weight. As for sulfone ilaprazole, larger AUC0→36 and AUC0→∞ were detected in female when compared with male (406.8  126.3 vs. 246.7  70.0 ng • h/ml, P = 0.007, and 606.7  224.5 vs. 332.0  117.1 ng • h/ml, P = 0.001), discrepancies were still significant after corrected by total body weight, P value were 0.017 and 0.010 respectively. The pharmacokinetics parameters of ilaprazole and ilaprazole sulfone were neither different across CYP2C19 genotype groups nor related to CYP3A phenotype. CL/F of ilaprazole were much smaller in women than in men even after adjusted by body weight, indicating great effect of gender on the pharmacokinetics of ilaprazole. CYP2C19 genotypes and CYP3A phenotypes did not affect the pharmacokinetics of ilaprazole or sulfone-ilaprazole.},
 year = {2015}
}

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TY  - JOUR
T1  - Gender, but Not CYP2C19 Genotypes and CYP3A Phenotypes, is a Major Determinant of Ilaprazole Pharmacokinetic
AU  - Shan Cao
AU  - Gan Zhou
AU  - Yao Chen
AU  - Dong Guo
AU  - Zhi-rong Tan
AU  - Lan Fan
AU  - Hai-tang Hu
AU  - Xiang-hong Qin
AU  - Hong-hao Zhou
AU  - Dong-sheng Ouyang
AU  - Wei Zhang
Y1  - 2015/01/27
PY  - 2015
N1  - https://doi.org/10.11648/j.ajls.s.2015030104.13
DO  - 10.11648/j.ajls.s.2015030104.13
T2  - American Journal of Life Sciences
JF  - American Journal of Life Sciences
JO  - American Journal of Life Sciences
SP  - 14
EP  - 20
PB  - Science Publishing Group
SN  - 2328-5737
UR  - https://doi.org/10.11648/j.ajls.s.2015030104.13
AB  - The purpose of the study was to assess the impact of CYP2C19 genotypes, CYP3A phenotypes and gender-related difference on the pharmacokinetics of new proton pump inhibitor ilaprazole. Twenty-four healthy Chinese volunteers (age 24.0  1.9 years) were enrolled in an open-label study stratified for gender (12 males and 12 females) and their CYP2C19 genotype (12 of CYP2C19*1/*1 and 12 of CYP2C19*1/*2 or *1/*3). After a single 10-mg dose of ilaprazole was administrated, blood samples were collected at time 0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36h from all subjects. Ilaprazole and its metabolite sulfone-ilaprazole plasma concentrations were measured using the well-validated HPLC/MS/MS method. CYP3A phenotype was determined by the classic CYP3A probe drug midazolam one week after the clinical trial. The kinetics characteristics of ilaprazole and sulfone-ilaprazole were significantly influenced by gender. The clearance/systemic bioavailability (CL/F) of ilaprazole was much lower in female than in male (2.5  1.0 versus 3.7  1.6 h-1, P = 0.029), difference became more significant even after corrected by body weight (P = 0.008). However, the differences on half-life, AUC0-36 and AUC0→∞ of ilaprazole between genders were not significantly after normalized by body weight. As for sulfone ilaprazole, larger AUC0→36 and AUC0→∞ were detected in female when compared with male (406.8  126.3 vs. 246.7  70.0 ng • h/ml, P = 0.007, and 606.7  224.5 vs. 332.0  117.1 ng • h/ml, P = 0.001), discrepancies were still significant after corrected by total body weight, P value were 0.017 and 0.010 respectively. The pharmacokinetics parameters of ilaprazole and ilaprazole sulfone were neither different across CYP2C19 genotype groups nor related to CYP3A phenotype. CL/F of ilaprazole were much smaller in women than in men even after adjusted by body weight, indicating great effect of gender on the pharmacokinetics of ilaprazole. CYP2C19 genotypes and CYP3A phenotypes did not affect the pharmacokinetics of ilaprazole or sulfone-ilaprazole.
VL  - 3
IS  - 1-4
ER  -

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