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Trimethoprim-metformin interaction and its genetic modulation by OCT2 and MATE1 transporters

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Trimethoprim-metformin interaction and its genetic modulation by OCT2 and MATE1 transporters. / Grün, Barbara; Kiessling, Michael K; Burhenne, Jürgen; Riedel, Klaus-Dieter; Weiss, Johanna; Rauch, Geraldine; Haefeli, Walter E; Czock, David.

In: BRIT J CLIN PHARMACO, Vol. 76, No. 5, 11.2013, p. 787-796.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Grün, B, Kiessling, MK, Burhenne, J, Riedel, K-D, Weiss, J, Rauch, G, Haefeli, WE & Czock, D 2013, 'Trimethoprim-metformin interaction and its genetic modulation by OCT2 and MATE1 transporters', BRIT J CLIN PHARMACO, vol. 76, no. 5, pp. 787-796. https://doi.org/10.1111/bcp.12079

APA

Grün, B., Kiessling, M. K., Burhenne, J., Riedel, K-D., Weiss, J., Rauch, G., Haefeli, W. E., & Czock, D. (2013). Trimethoprim-metformin interaction and its genetic modulation by OCT2 and MATE1 transporters. BRIT J CLIN PHARMACO, 76(5), 787-796. https://doi.org/10.1111/bcp.12079

Vancouver

Grün B, Kiessling MK, Burhenne J, Riedel K-D, Weiss J, Rauch G et al. Trimethoprim-metformin interaction and its genetic modulation by OCT2 and MATE1 transporters. BRIT J CLIN PHARMACO. 2013 Nov;76(5):787-796. https://doi.org/10.1111/bcp.12079

Bibtex

@article{fd3f621cc98e44ad99a6d1977dfea867,
title = "Trimethoprim-metformin interaction and its genetic modulation by OCT2 and MATE1 transporters",
abstract = "AIMS: Metformin pharmacokinetics depends on the presence and activity of membrane-bound drug transporters and may be affected by transport inhibitors. The aim of this study was to investigate the effects of trimethoprim on metformin pharmacokinetics and genetic modulation by organic cation transporter 2 (OCT2) and multidrug and toxin extrusion 1 (MATE1) polymorphisms.METHODS: Twenty-four healthy volunteers received metformin 500 mg three times daily for 10 days and trimethoprim 200 mg twice daily from day 5 to 10. Effects of trimethoprim on steady-state metformin pharmacokinetics were analysed.RESULTS: In the population as a whole, trimethoprim significantly reduced the apparent systemic metformin clearance (CL/F) from 74 to 54 l h(-1) and renal metformin clearance from 31 to 21 l h(-1) , and prolonged half-life from 2.7 to 3.6 h (all P < 0.01). This resulted in an increase in the maximal plasma concentration by 38% and in the area under the plasma concentration-time curve by 37%. In volunteers polymorphic for both OCT2 and MATE1, trimethoprim had no relevant inhibitory effects on metformin kinetics. Trimethoprim was associated with a decrease in creatinine clearance from 133 to 106 ml min(-1) (P < 0.01) and an increase in plasma lactate from 0.94 to 1.2 mmol l(-1) (P = 0.016).CONCLUSIONS: The extent of inhibition by trimethoprim was moderate, but might be clinically relevant in patients with borderline renal function or high-dose metformin.",
keywords = "Adult, Anti-Infective Agents, Urinary, Area Under Curve, Creatinine, Drug Interactions, Half-Life, Humans, Hypoglycemic Agents, Lactic Acid, Male, Metformin, Middle Aged, Molecular Sequence Data, Organic Cation Transport Proteins, Polymorphism, Single Nucleotide, Trimethoprim, Young Adult, Comparative Study, Controlled Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't",
author = "Barbara Gr{\"u}n and Kiessling, {Michael K} and J{\"u}rgen Burhenne and Klaus-Dieter Riedel and Johanna Weiss and Geraldine Rauch and Haefeli, {Walter E} and David Czock",
note = "{\textcopyright} 2013 The Authors. British Journal of Clinical Pharmacology {\textcopyright} 2013 The British Pharmacological Society.",
year = "2013",
month = nov,
doi = "10.1111/bcp.12079",
language = "English",
volume = "76",
pages = "787--796",
journal = "BRIT J CLIN PHARMACO",
issn = "0306-5251",
publisher = "Wiley-Blackwell",
number = "5",

}

RIS

TY - JOUR

T1 - Trimethoprim-metformin interaction and its genetic modulation by OCT2 and MATE1 transporters

AU - Grün, Barbara

AU - Kiessling, Michael K

AU - Burhenne, Jürgen

AU - Riedel, Klaus-Dieter

AU - Weiss, Johanna

AU - Rauch, Geraldine

AU - Haefeli, Walter E

AU - Czock, David

N1 - © 2013 The Authors. British Journal of Clinical Pharmacology © 2013 The British Pharmacological Society.

PY - 2013/11

Y1 - 2013/11

N2 - AIMS: Metformin pharmacokinetics depends on the presence and activity of membrane-bound drug transporters and may be affected by transport inhibitors. The aim of this study was to investigate the effects of trimethoprim on metformin pharmacokinetics and genetic modulation by organic cation transporter 2 (OCT2) and multidrug and toxin extrusion 1 (MATE1) polymorphisms.METHODS: Twenty-four healthy volunteers received metformin 500 mg three times daily for 10 days and trimethoprim 200 mg twice daily from day 5 to 10. Effects of trimethoprim on steady-state metformin pharmacokinetics were analysed.RESULTS: In the population as a whole, trimethoprim significantly reduced the apparent systemic metformin clearance (CL/F) from 74 to 54 l h(-1) and renal metformin clearance from 31 to 21 l h(-1) , and prolonged half-life from 2.7 to 3.6 h (all P < 0.01). This resulted in an increase in the maximal plasma concentration by 38% and in the area under the plasma concentration-time curve by 37%. In volunteers polymorphic for both OCT2 and MATE1, trimethoprim had no relevant inhibitory effects on metformin kinetics. Trimethoprim was associated with a decrease in creatinine clearance from 133 to 106 ml min(-1) (P < 0.01) and an increase in plasma lactate from 0.94 to 1.2 mmol l(-1) (P = 0.016).CONCLUSIONS: The extent of inhibition by trimethoprim was moderate, but might be clinically relevant in patients with borderline renal function or high-dose metformin.

AB - AIMS: Metformin pharmacokinetics depends on the presence and activity of membrane-bound drug transporters and may be affected by transport inhibitors. The aim of this study was to investigate the effects of trimethoprim on metformin pharmacokinetics and genetic modulation by organic cation transporter 2 (OCT2) and multidrug and toxin extrusion 1 (MATE1) polymorphisms.METHODS: Twenty-four healthy volunteers received metformin 500 mg three times daily for 10 days and trimethoprim 200 mg twice daily from day 5 to 10. Effects of trimethoprim on steady-state metformin pharmacokinetics were analysed.RESULTS: In the population as a whole, trimethoprim significantly reduced the apparent systemic metformin clearance (CL/F) from 74 to 54 l h(-1) and renal metformin clearance from 31 to 21 l h(-1) , and prolonged half-life from 2.7 to 3.6 h (all P < 0.01). This resulted in an increase in the maximal plasma concentration by 38% and in the area under the plasma concentration-time curve by 37%. In volunteers polymorphic for both OCT2 and MATE1, trimethoprim had no relevant inhibitory effects on metformin kinetics. Trimethoprim was associated with a decrease in creatinine clearance from 133 to 106 ml min(-1) (P < 0.01) and an increase in plasma lactate from 0.94 to 1.2 mmol l(-1) (P = 0.016).CONCLUSIONS: The extent of inhibition by trimethoprim was moderate, but might be clinically relevant in patients with borderline renal function or high-dose metformin.

KW - Adult

KW - Anti-Infective Agents, Urinary

KW - Area Under Curve

KW - Creatinine

KW - Drug Interactions

KW - Half-Life

KW - Humans

KW - Hypoglycemic Agents

KW - Lactic Acid

KW - Male

KW - Metformin

KW - Middle Aged

KW - Molecular Sequence Data

KW - Organic Cation Transport Proteins

KW - Polymorphism, Single Nucleotide

KW - Trimethoprim

KW - Young Adult

KW - Comparative Study

KW - Controlled Clinical Trial

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1111/bcp.12079

DO - 10.1111/bcp.12079

M3 - SCORING: Journal article

C2 - 23305245

VL - 76

SP - 787

EP - 796

JO - BRIT J CLIN PHARMACO

JF - BRIT J CLIN PHARMACO

SN - 0306-5251

IS - 5

ER -