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

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Abstract

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.

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Acknowledgments

We wish to thank Howard McLeod, PharmD for reviewing this manuscript.

Funding

This study was funded in part by the American College of Clinical Pharmacy - Merck Cardiovascular Fellowship (KDL), NIH 5K23DK64888 (MSJ), and the Intramural Research Program of the NIH and NIEHS (J.B. and J.A.G.).

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Correspondence to Melanie S. Joy.

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Joy, M.S., Dornbrook-Lavender, K., Blaisdell, J. et al. CYP2C9 genotype and pharmacodynamic responses to losartan in patients with primary and secondary kidney diseases. Eur J Clin Pharmacol 65, 947–953 (2009). https://doi.org/10.1007/s00228-009-0707-7

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  • DOI: https://doi.org/10.1007/s00228-009-0707-7

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