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Jørgen Frøkiær

Genetic Polymorphisms in Organic Cation Transporter 1 Attenuates Hepatic Metformin Exposure in Humans

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Genetic Polymorphisms in Organic Cation Transporter 1 Attenuates Hepatic Metformin Exposure in Humans. / Sundelin, Elias; Gormsen, Lars Christian; Jensen, Jonas Brorson; Vendelbo, Mikkel Holm; Jakobsen, Steen; Munk, Ole Lajord; Christensen, Mette Marie Hougaard; Brøsen, Kim; Frøkiaer, Jørgen; Jessen, Niels.

In: Clinical Pharmacology and Therapeutics, Vol. 102, No. 5, 11.2017, p. 841-848.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

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@article{d08ca43d25804c52a3d8d52f11173378,
title = "Genetic Polymorphisms in Organic Cation Transporter 1 Attenuates Hepatic Metformin Exposure in Humans",
abstract = "Metformin has been used successfully to treat type 2 diabetes for decades. However, the efficacy of the drug varies considerably from patient to patient and this may in part be due to its pharmacokinetic properties. The aim of this study was to examine if common polymorphisms in SLC22A1, encoding the transporter protein OCT1, affect the hepatic distribution of metformin in humans. We performed non-invasive (11) C-metformin PET/CT to determine hepatic exposure in 12 subjects genotyped for variants in SLC22A1. Hepatic distribution of metformin was significantly reduced after oral intake in carriers of M420del and R61C variants in SLC22A1 without being associated with changes in circulating levels of metformin. Our data show that genetic polymorphisms in transporter proteins cause variation in hepatic exposure to metformin, and it demonstrates the application of novel imaging techniques to investigate pharmacogenetic properties in humans. This article is protected by copyright. All rights reserved.",
keywords = "Journal Article",
author = "Elias Sundelin and Gormsen, {Lars Christian} and Jensen, {Jonas Brorson} and Vendelbo, {Mikkel Holm} and Steen Jakobsen and Munk, {Ole Lajord} and Christensen, {Mette Marie Hougaard} and Kim Br{\o}sen and J{\o}rgen Fr{\o}kiaer and Niels Jessen",
note = "{\textcopyright} 2017 American Society for Clinical Pharmacology and Therapeutics.",
year = "2017",
month = nov,
doi = "10.1002/cpt.701",
language = "English",
volume = "102",
pages = "841--848",
journal = "Clinical Pharmacology and Therapeutics",
issn = "0009-9236",
publisher = "JohnWiley & Sons, Inc.",
number = "5",

}

RIS

TY - JOUR

T1 - Genetic Polymorphisms in Organic Cation Transporter 1 Attenuates Hepatic Metformin Exposure in Humans

AU - Sundelin, Elias

AU - Gormsen, Lars Christian

AU - Jensen, Jonas Brorson

AU - Vendelbo, Mikkel Holm

AU - Jakobsen, Steen

AU - Munk, Ole Lajord

AU - Christensen, Mette Marie Hougaard

AU - Brøsen, Kim

AU - Frøkiaer, Jørgen

AU - Jessen, Niels

N1 - © 2017 American Society for Clinical Pharmacology and Therapeutics.

PY - 2017/11

Y1 - 2017/11

N2 - Metformin has been used successfully to treat type 2 diabetes for decades. However, the efficacy of the drug varies considerably from patient to patient and this may in part be due to its pharmacokinetic properties. The aim of this study was to examine if common polymorphisms in SLC22A1, encoding the transporter protein OCT1, affect the hepatic distribution of metformin in humans. We performed non-invasive (11) C-metformin PET/CT to determine hepatic exposure in 12 subjects genotyped for variants in SLC22A1. Hepatic distribution of metformin was significantly reduced after oral intake in carriers of M420del and R61C variants in SLC22A1 without being associated with changes in circulating levels of metformin. Our data show that genetic polymorphisms in transporter proteins cause variation in hepatic exposure to metformin, and it demonstrates the application of novel imaging techniques to investigate pharmacogenetic properties in humans. This article is protected by copyright. All rights reserved.

AB - Metformin has been used successfully to treat type 2 diabetes for decades. However, the efficacy of the drug varies considerably from patient to patient and this may in part be due to its pharmacokinetic properties. The aim of this study was to examine if common polymorphisms in SLC22A1, encoding the transporter protein OCT1, affect the hepatic distribution of metformin in humans. We performed non-invasive (11) C-metformin PET/CT to determine hepatic exposure in 12 subjects genotyped for variants in SLC22A1. Hepatic distribution of metformin was significantly reduced after oral intake in carriers of M420del and R61C variants in SLC22A1 without being associated with changes in circulating levels of metformin. Our data show that genetic polymorphisms in transporter proteins cause variation in hepatic exposure to metformin, and it demonstrates the application of novel imaging techniques to investigate pharmacogenetic properties in humans. This article is protected by copyright. All rights reserved.

KW - Journal Article

U2 - 10.1002/cpt.701

DO - 10.1002/cpt.701

M3 - Journal article

C2 - 28380657

VL - 102

SP - 841

EP - 848

JO - Clinical Pharmacology and Therapeutics

JF - Clinical Pharmacology and Therapeutics

SN - 0009-9236

IS - 5

ER -