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

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.

• Authors: 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
• Journal: European journal of clinical pharmacology (Eur J Clin Pharmacol) Vol. 65 Issue 9 Pg. 947-53 (Sep 2009) ISSN: 1432-1041 [Electronic] Germany
• PMID: 19669737 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't)

Chemical References

• Angiotensin II Type 1 Receptor Blockers
• Antihypertensive Agents
• CYP2C9 protein, human
• Cytochrome P-450 CYP2C9
• Aryl Hydrocarbon Hydroxylases
• Losartan

Topics

• Adult
• Aged
• Angiotensin II Type 1 Receptor Blockers (pharmacology)
• Antihypertensive Agents (pharmacology)
• Aryl Hydrocarbon Hydroxylases (genetics)
• Blood Pressure (drug effects)
• Cytochrome P-450 CYP2C9
• Female
• Gene Frequency
• Genotype
• Glomerular Filtration Rate (drug effects)
• Humans
• Kidney Failure, Chronic (etiology, physiopathology)
• Losartan (pharmacology)
• Male
• Middle Aged
• Polymorphism, Single Nucleotide
• Proteinuria (prevention & control)
• White People (genetics)