TY - JOUR
T1 - CYP2C9*3 allelic variant is associated with metabolism of irbesartan in Chinese population.
AU - Hong, Xiumei
AU - Zhang, Shanchun
AU - Mao, Guangyun
AU - Jiang, Shanqun
AU - Zhang, Yan
AU - Yu, Yunxian
AU - Tang, Genfu
AU - Xing, Houxun
AU - Xu, Xiping
N1 - Funding Information:
Acknowledgements This study was supported in part by Anhui Provincial Ministry of Education, Anhui Medical University Biomedical Institute. We would like to thank the faculty and staff of the Anhui Medical University and of the Program of Population Genetics at Harvard School of Public Health. We are also grateful to all study participants and their families for their assistance and cooperation. We would like to thank Dr. Scott Venners and Dr. Xiaobin Wang for their careful editing of the manuscript. This study was conducted in accordance with the current regulations of People’s Republic of China and was approved by the institutional review board at Anhui Medical University. None of the authors claims any conflict of interest.
PY - 2005/10
Y1 - 2005/10
N2 - OBJECTIVE: There is considerable variability in the individual pharmaceutical dosages required to achieve optimal therapeutic effects, which may be due to environmental or genetic factors. The objective of this study was to test the presence of the CYP2C9*3 allelic variant in the Chinese population and to investigate the association of this variant with both metabolism and therapeutic efficacy of irbesartan on essential hypertension. METHODS: In this study, we enrolled 711 subjects from Taihu County and 376 subjects from Dongzhi County in Anhui Province, China. All subjects received a single oral dose of 150 mg irbesartan daily for 28 days. The plasma concentration of irbesartan at 24 h after dosing on the 27th day and at 6 h after dosing on the 28th day was detected using fluorescence-high-performance liquid chromatography. CYP2C9 genotypes were determined using polymerase chain reaction-restriction fragment length polymorphism. RESULTS: No CYP2C9*2 allele was found in 235 Chinese samples and was removed from further study. The mean frequency of the CYP2C9*3 allele was 3.65%, while no CYP2C9*3/*3 genotype was detected. Multiple linear regression analyses revealed that the CYP2C9*3 allele carriers had significantly higher irbesartan concentrations in plasma at 6 h (Taihu: P < 0.0001; Dongzhi: P = 0.03) and 24 h (Taihu: P < 0.0001; Dongzhi: P = 0.00013) after dosing. No significant association was found between the CYP2C9*3 allelic variant and the therapeutic effect of irbesartan on essential hypertension. CONCLUSION: Our study suggests that the CYP2C9*3 plays an important role in the metabolism of irbesartan and/or is in linkage disequilibrium with another potential CYP2C9 allele, both of which possibly modify the pharmacokinetics of irbesartan.
AB - OBJECTIVE: There is considerable variability in the individual pharmaceutical dosages required to achieve optimal therapeutic effects, which may be due to environmental or genetic factors. The objective of this study was to test the presence of the CYP2C9*3 allelic variant in the Chinese population and to investigate the association of this variant with both metabolism and therapeutic efficacy of irbesartan on essential hypertension. METHODS: In this study, we enrolled 711 subjects from Taihu County and 376 subjects from Dongzhi County in Anhui Province, China. All subjects received a single oral dose of 150 mg irbesartan daily for 28 days. The plasma concentration of irbesartan at 24 h after dosing on the 27th day and at 6 h after dosing on the 28th day was detected using fluorescence-high-performance liquid chromatography. CYP2C9 genotypes were determined using polymerase chain reaction-restriction fragment length polymorphism. RESULTS: No CYP2C9*2 allele was found in 235 Chinese samples and was removed from further study. The mean frequency of the CYP2C9*3 allele was 3.65%, while no CYP2C9*3/*3 genotype was detected. Multiple linear regression analyses revealed that the CYP2C9*3 allele carriers had significantly higher irbesartan concentrations in plasma at 6 h (Taihu: P < 0.0001; Dongzhi: P = 0.03) and 24 h (Taihu: P < 0.0001; Dongzhi: P = 0.00013) after dosing. No significant association was found between the CYP2C9*3 allelic variant and the therapeutic effect of irbesartan on essential hypertension. CONCLUSION: Our study suggests that the CYP2C9*3 plays an important role in the metabolism of irbesartan and/or is in linkage disequilibrium with another potential CYP2C9 allele, both of which possibly modify the pharmacokinetics of irbesartan.
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U2 - 10.1007/s00228-005-0976-8
DO - 10.1007/s00228-005-0976-8
M3 - Article
C2 - 16094537
AN - SCOPUS:33645340776
SN - 0031-6970
VL - 61
SP - 627
EP - 634
JO - European journal of clinical pharmacology
JF - European journal of clinical pharmacology
IS - 9
ER -