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Joy, M.S. et al.

Melanie S. Joy, Kimberly Dornbrook-Lavender, Joyce Blaisdell, Tandrea Hilliard, Tammy Boyette, Yichun Hu, Susan L. Hogan, Corina Candiani, Ronald J. Falk, Joyce A. Goldstein,

CYP2C9 genotype and pharmacodynamic responses to losartan in patients with primary and secondary kidney diseases.

BACKGROUND: Losartan is used for anti-proteinuric as well as blood pressure effects in chronic kidney disease (CKD). It is metabolized by cytochrome P450 (CYP) 2C9 to active E-3174. Single nucleotide polymorphisms in CYP2C9 that reduce catalytic activity could reduce clinical benefits. AIM: The study aims were to determine whether CYP2C9 variant alleles (*2 and *3) altered urinary protein excretion, glomerular filtration rate, and blood pressure in Caucasian patients prescribed losartan. METHODS: Differences between baseline and 6-month follow-up outcomes were compared by CYP2C9 genotypes in 59 patients using unpaired t test or Mann-Whitney U test. RESULTS: 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 vs. -3.2 +/- 10.6 mmHg; p = 0.043) and systolic blood pressure (16.2 +/- 27.1 vs. -5.5 +/- 17.5 mmHg; p = 0.044) with CYP2C9 variants. CONCLUSION: These preliminary results suggest a possible influence of CYP2C9 genotype on proteinuria and blood pressure in Caucasian CKD patients treated with losartan.[1]

References

CYP2C9 genotype and pharmacodynamic responses to losartan in patients with primary and secondary kidney diseases. Joy, M.S., Dornbrook-Lavender, K., Blaisdell, J., Hilliard, T., Boyette, T., Hu, Y., Hogan, S.L., Candiani, C., Falk, R.J., Goldstein, J.A. Eur. J. Clin. Pharmacol. (2009) [Pubmed]

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