Gender, but Not CYP2C19 Genotypes and CYP3A Phenotypes, is a Major Determinant of Ilaprazole Pharmacokinetic
American Journal of Life Sciences
Volume 3, Issue 1-4, January 2015, Pages: 14-20
Received: Sep. 16, 2014; Accepted: Nov. 24, 2014; Published: Jan. 27, 2015
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Authors
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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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.
Keywords
CYP2C19, CYP3A Phenotype, Ilaprazole, Pharmacokinetics, Gender Difference
To cite this article
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, Gender, but Not CYP2C19 Genotypes and CYP3A Phenotypes, is a Major Determinant of Ilaprazole Pharmacokinetic, American Journal of Life Sciences. Special Issue: Pharmacogenomics & Personalized Medicine. Vol. 3, No. 1-4, 2015, pp. 14-20. doi: 10.11648/j.ajls.s.2015030104.13
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