CYP2C9 genotype and pharmacodynamic responses to losartan in patients with primary and secondary kidney diseases.
CYP2C9 genotype and pharmacodynamic responses to losartan in patients with primary and secondary kidney diseases.
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DOI：
10.1007/s00228-009-0707-7
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发表时间：
2009-09
影响因子：
2.9
通讯作者：
Goldstein, Joyce A.
中科院分区：
文献类型：
--
作者：
Joy, Melanie S.;Dornbrook-Lavender, Kimberly;Blaisdell, Joyce;Hilliard, Tandrea;Boyette, Tammy;Hu, Yichun;Hogan, Susan L.;Candiani, Corina;Falk, Ronald J.;Goldstein, Joyce A.
Losartan is used for anti-proteinuric as well as blood pressure effects in chronic kidney disease (CKD). It is metabolized by cytochrome P450 2C9 to active E-3174. Single nucleotide polymorphisms in CYP2C9 that reduce catalytic activity could reduce clinical benefits. The study aims were to determine whether CYP2C9 variant alleles (*2 and *3) altered urinary protein excretion, glomerular filtration rate, and blood pressure in Caucasians prescribed losartan. Differences between baseline and six-month follow-up outcomes were compared by CYP2C9 genotypes in 59 patients using unpaired T-test or Mann Whitney U test. Primary renal disease patients had a trend toward less favorable antiproteinuric response (−31.7±156 vs −125±323%; p=0.123) when carrying variant alleles. Patients with secondary renal diseases had less favorable diastolic blood pressure (9.8±16.0 mm Hg vs −3.2±10.6 mm Hg; p=0.043) and systolic blood pressure (16.2±27.1 mm Hg vs −5.5±17.5 mm Hg; p=0.044) with CYP2C9 variants. Preliminary results suggest a possible influence of CYP2C9 genotype on proteinuria and blood pressure in Caucasian CKD patients treated with losartan.
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