Premium
Impact of genetic polymorphisms in the gene coding for sodium potassium dichloride cotransporter (NKCC2) and serum glucocorticoid kinase (SGK1) for pharmacodynamics of furosemide
Author(s) -
Sehrt D.,
Vormfelde S.,
Toliat M.,
Nürnberg P.,
Schirmer M.,
Brockmöller J.
Publication year - 2005
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/j.clpt.2004.12.107
Subject(s) - furosemide , excretion , endocrinology , urine , medicine , genotype , chemistry , sodium , potassium , sgk1 , pharmacodynamics , glucocorticoid receptor , pharmacokinetics , pharmacology , glucocorticoid , gene , biochemistry , organic chemistry
Background /Aims We were interested whether the known inter‐individual variability in furosemide effects might be related with genetic polymorphisms in the sodium potassium dichloride cotransporter (NKCC2) and in serum and glucocorticoid regulated kinase (SGK1) which regulates NKCC2. Methods In an open‐label single dose study 93 healthy male volunteers received a single dose of 80 mg furosemide. Urine volume, sodium, chloride, potassium and calcium excretion was measured in 9 intervals between 0 and 24 hours after drug administration. Results A total of 10 informative polymorphisms in the NKCC2 gene were analyzed but none of them was significantly associated with the furosemide effects. However, one intronically localized guanine/deletion (G/del) polymorphism in the SGK1 gene was associated with Na, Cl, K, and Ca urinary excretion. Na excretion in the first 3 hours after furosemide was 198, 247, and 273 mmol in G/G, G/del and del/del, respectively (p=0.002, ANOVA). This genotype‐related difference was also seen in the cumulative 24‐hour urine. Correspondingly, Cl excretion was also correlated with the SGK1 polymorphism (p= 0.001 for the 3h interval) and there were also differences in K and Ca excretion. We did however not observe significant influences on the urine volumes. Conclusions The finding with SKG1 might have great medical relevance but requires further confirmation because of the explorative nature of our investigation. Clinical Pharmacology & Therapeutics (2005) 77 , P57–P57; doi: 10.1016/j.clpt.2004.12.107