Influence of SLCO1B3 gene polymorphism on the pharmacokinetics of digoxin in terminal renal failure

Drug Metabolism and Pharmacokinetics
Masayuki TsujimotoYasufumi Sawada

Abstract

Digoxin (DX) is mainly excreted unchanged in the urine. In patients undergoing hemodialysis (HD patients), the relative contribution of hepatic elimination is increased. DX is a substrate of OATP1B3 (SLCO1B3), expressed on the sinusoidal membranes of hepatocytes in humans. Therefore, we investigated the relationship between SLCO1B3 gene polymorphisms and the value of trough concentration-to-dose ratio (C/D ratio) of DX in HD patients. We investigated two deletion polymorphisms in complete linkage disequilibrium (-28 to -11 and -7 to -4) and two SNPs in complete linkage disequilibrium (T334G and G699A). Blood was sampled 62-72 hours after the oral administration of DX. The C/D ratio of DX was lower in patients with the deletion allele than in those homozygous for the insertion allele, and was lower in patients with the 334T/669G allele than in those homozygous for the 334G/699A allele, although the differences were not statistically significant. The C/D ratio of DX was significantly higher in patients with homozygous for the insert-variant allele (median: 121.8 (ng/mL)/(mg/week/kg), range: 92.5-259.4 (ng/mL)/(mg/week/kg) than in others (median: 93.4 (ng/mL)/(mg/week/kg), range: 66.5-154.3 (ng/mL)/(mg/week/kg)). In conclusion, th...Continue Reading

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Citations

Mar 9, 2011·Drug Metabolism and Pharmacokinetics·Masato TaguchiYukiya Hashimoto
Dec 22, 2011·Drug Metabolism and Pharmacokinetics·Takeo Nakanishi, Ikumi Tamai
Nov 7, 2012·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Sabrina AngeliniGuido Biasco
Oct 15, 2011·British Journal of Clinical Pharmacology·Sin Chi ChewBalram Chowbay
Dec 6, 2011·Basic & Clinical Pharmacology & Toxicology·Vinicius de A SorticaMara H Hutz
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Jun 11, 2019·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Yingmin NieChunshan Gui
Apr 24, 2014·Molecular Pharmaceutics·Elnaz GozalpourJan B Koenderink

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