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The pharmacogenetic...
The pharmacogenetics of metformin and its impact on plasma metformin steady-state levels and glycosylated hemoglobin A1c
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- Christensen, Mette M H (författare)
- University of So Denmark
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- Brasch-Andersen, Charlotte (författare)
- Odense University Hospital
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- Green, Henrik (författare)
- KTH,Linköpings universitet,Klinisk farmakologi,Hälsouniversitetet,Genteknologi,Science for Life Laboratory, SciLifeLab,Division of Drug Research, Department of Medicine and Health Sciences, Clinical Pharmacology, Faculty of Health Sciences, Linköping University, Linköpingg
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- Nielsen, Flemming (författare)
- University of So Denmark
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- Damkier, Per (författare)
- Odense University Hospital
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- Beck-Nielsen, Henning (författare)
- Odense University Hospital
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- Brosen, Kim (författare)
- University of So Denmark
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(creator_code:org_t)
- Lippincott, Williams and Wilkins, 2011
- 2011
- Engelska.
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Ingår i: Pharmacogenetics & Genomics. - : Lippincott, Williams and Wilkins. - 1744-6872 .- 1744-6880. ; 21:12, s. 837-850
- Relaterad länk:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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https://urn.kb.se/re...
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Abstract
Ämnesord
Stäng
- Objective The aim of this study was to evaluate the effect of genetic variations in OCT1, OCT2, MATE1, MATE 2, and PMAT on the trough steady-state plasma concentration of metformin and hemoglobin A1c (Hb1Ac). less thanbrgreater than less thanbrgreater thanMethod The South Danish Diabetes Study was a 2 x 2 x 2 factorial, prospective, randomized, double-blind, placebo-controlled, multicentre study. One hundred and fifty-nine patients received 1 g of metformin, twice daily continuously, and 415 repeated plasma metformin measurements were obtained after 3, 6, and 9 months of treatment. less thanbrgreater than less thanbrgreater thanResults The mean trough steady-state metformin plasma concentration was estimated to be 576 ng/ml (range, 54-4133 ng/ml, rho = 0.55) and correlated to the number of reduced function alleles in OCT1 (none, one or two: 642, 542, 397 ng/ml; P = 0.001). The absolute decrease in Hb1Ac both initially and long term was also correlated to the number of reduced function alleles in OCT1 resulting in diminished pharmacodynamic effect of metformin after 6 and 24 months. less thanbrgreater than less thanbrgreater thanConclusion In a large cohort of type 2 diabetics, we either confirm or show for the first time: (a) an enormous 80-fold) variability in trough steady-state metformin plasma concentration, (b) OCT1 activity affects metformin steady-state pharmacokinetics, and (c) OCT1 genotype has a bearing on HbA1c during metformin treatment.
Ämnesord
- NATURVETENSKAP -- Biologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences (hsv//eng)
Nyckelord
- MATE1
- MATE2
- metformin
- OCT1
- OCT2
- personalized medicine
- pharmacogenetics
- PMAT
- steady state
- type 2 diabetes
- MEDICINE
- MEDICIN
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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