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

Eur J Clin Pharmacol. 2009 Sep;65(9):947-53. doi: 10.1007/s00228-009-0707-7. Epub 2009 Aug 11.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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
  • Kidney Failure, Chronic / physiopathology*
  • Losartan / pharmacology*
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Proteinuria / prevention & control*
  • White People / genetics

Substances

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