CYP2C9 Ile359Leu polymorphism, plasma irbesartan concentration and acute blood pressure reductions in response to irbesartan treatment in Chinese hypertensive patients

G. Chen, S. Jiang, G. Mao, S. Zhang, Xiumei Hong, G. Tang, Z. Li, X. Liu, Y. Zhang, H. Xing, B. Wang, Y. Yu, Xiping Xu

Research output: Contribution to journalArticle

Abstract

Our previous study demonstrated that the CYP2C9*3 gene variant was significantly associated with elevated plasma irbesartan concentration and blood pressure decline, assessed by a 4-week follow-up and revisit following daily administration of irbesartan. We conducted a further analysis to examine the acute effects of the CYP2C9 polymorphism on plasma concentration and blood pressure through remeasurement 6 h after administration of irbesartan. We used an extreme-sampling approach by selecting individuals from the top and bottom deciles of blood pressure response residuals to irbesartan from the previous study population in Anhui, Taihu, and Dongzhi Counties, in China. A total of 196 subjects were available for the analysis. Pre- and posttreatment systolic and diastolic blood pressures (SBP and DBP), and venous blood samples (0.5, 2, and 6 h following the first treatment) were collected from each individual. Plasma irbesartan concentrations were determined by a standard HPLC/fluorescence method. The observed frequencies were 97.7% for CYP2C9*1 (Ile359) and 23% for CYP2C9*3 (Leu359). Subjects with the CYP2C9*1/CYP2C9*3 genotype had significantly higher plasma irbesartan concentrations when compared with those with the CYP2C9*1/CYP2C9*1 genotype (β ± SE = 81 ± 36) and greater DBP response (β ± SE = 5.6 ± 2.5 mmHg) at the 6-h time point after adjusting for important confounders. Our finding suggests that the CYP2C9*3 gene variant significantly alters the plasma concentration and acute DBP response at the 6-h point following irbesartan treatment in Chinese hypertensive patients.

Original languageEnglish (US)
Pages (from-to)19-24
Number of pages6
JournalMethods and Findings in Experimental and Clinical Pharmacology
Volume28
Issue number1
DOIs
StatePublished - Jan 2006
Externally publishedYes

Fingerprint

irbesartan
Blood Pressure
Therapeutics
Genotype
Cytochrome P-450 CYP2C9

Keywords

  • Blood pressure
  • CYP2C9 gene
  • Drug concentration
  • Gene polymorphism
  • Irbesartan
  • Pharmacogenetics

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

CYP2C9 Ile359Leu polymorphism, plasma irbesartan concentration and acute blood pressure reductions in response to irbesartan treatment in Chinese hypertensive patients. / Chen, G.; Jiang, S.; Mao, G.; Zhang, S.; Hong, Xiumei; Tang, G.; Li, Z.; Liu, X.; Zhang, Y.; Xing, H.; Wang, B.; Yu, Y.; Xu, Xiping.

In: Methods and Findings in Experimental and Clinical Pharmacology, Vol. 28, No. 1, 01.2006, p. 19-24.

Research output: Contribution to journalArticle

Chen, G. ; Jiang, S. ; Mao, G. ; Zhang, S. ; Hong, Xiumei ; Tang, G. ; Li, Z. ; Liu, X. ; Zhang, Y. ; Xing, H. ; Wang, B. ; Yu, Y. ; Xu, Xiping. / CYP2C9 Ile359Leu polymorphism, plasma irbesartan concentration and acute blood pressure reductions in response to irbesartan treatment in Chinese hypertensive patients. In: Methods and Findings in Experimental and Clinical Pharmacology. 2006 ; Vol. 28, No. 1. pp. 19-24.
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AU - Mao, G.

AU - Zhang, S.

AU - Hong, Xiumei

AU - Tang, G.

AU - Li, Z.

AU - Liu, X.

AU - Zhang, Y.

AU - Xing, H.

AU - Wang, B.

AU - Yu, Y.

AU - Xu, Xiping

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AB - Our previous study demonstrated that the CYP2C9*3 gene variant was significantly associated with elevated plasma irbesartan concentration and blood pressure decline, assessed by a 4-week follow-up and revisit following daily administration of irbesartan. We conducted a further analysis to examine the acute effects of the CYP2C9 polymorphism on plasma concentration and blood pressure through remeasurement 6 h after administration of irbesartan. We used an extreme-sampling approach by selecting individuals from the top and bottom deciles of blood pressure response residuals to irbesartan from the previous study population in Anhui, Taihu, and Dongzhi Counties, in China. A total of 196 subjects were available for the analysis. Pre- and posttreatment systolic and diastolic blood pressures (SBP and DBP), and venous blood samples (0.5, 2, and 6 h following the first treatment) were collected from each individual. Plasma irbesartan concentrations were determined by a standard HPLC/fluorescence method. The observed frequencies were 97.7% for CYP2C9*1 (Ile359) and 23% for CYP2C9*3 (Leu359). Subjects with the CYP2C9*1/CYP2C9*3 genotype had significantly higher plasma irbesartan concentrations when compared with those with the CYP2C9*1/CYP2C9*1 genotype (β ± SE = 81 ± 36) and greater DBP response (β ± SE = 5.6 ± 2.5 mmHg) at the 6-h time point after adjusting for important confounders. Our finding suggests that the CYP2C9*3 gene variant significantly alters the plasma concentration and acute DBP response at the 6-h point following irbesartan treatment in Chinese hypertensive patients.

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