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Pharmacogenetics of loop diuretics
Author(s) -
Vormfelde S. V.,
Zirk A.,
Westermann J.,
Torn M.,
Tuchen F.,
Toliat M. R.,
Brockmöller J.
Publication year - 2004
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.2003.11.239
Subject(s) - furosemide , bumetanide , diuretic , chemistry , pharmacogenetics , coefficient of variation , genetic variation , pharmacodynamics , pharmacokinetics , genetic variability , pharmacology , medicine , endocrinology , genotype , sodium , biochemistry , chromatography , cotransporter , gene , organic chemistry
Objective Genetic variability in pharmacokinetics and pharmacodynamics of diuretics is incompletely studied. We compared the extent of variability in different loop diuretics and determined to what extent this is influenced by polymorphisms in candidate genes. Methods Single oral doses of bumetanide 2 mg, furosemide 80 mg and torasemide 10 mg were given in two week intervals to 84 healthy male volunteers. Results Mean data (standard deviation) of volume, Na+ and K+ excretion are given in the Table. Variances were not significantly different between the three loop diuretics (equal variance test p> 0.05). Repeated measures ANOVA revealed interindividual variation amounting to 70, 43 and 53% of total variation for volume, Na+ and K+, respectively. In contrast, the within‐subject variation between the 3 study days amounted to only 1, 17 and 10% of total variation despite the use of three different loop diuretics. Polymorphisms in the G‐protein subunit 3 (GNB3) and alpha adducin (ADD1) were not correlated with the 24 h excretion of volume, Na+ or K+. Conclusions A high interindividual variation combined with low intraindividual variation may be explained by genetic polymorphisms in several of the transport and signaling proteins implicated in the action of diuretics. Clinical Pharmacology & Therapeutics (2004) 75 , P63–P63; doi: 10.1016/j.clpt.2003.11.239Urine volume (L/24 h) Na+ (mmol/24 h) K+ (mmol/24 h)Bumetanide 3.77 (0.90) 316 (49) 42 (10) Furosemide 3.75 (0.96) 302 (72) 45 (12) Torasemide 3.21 (0.96) 225 (52) 33 (9)