Interaction of beta-blockers with the renal uptake transporter OCT2

Diabetes Obes Metab. 2009 Nov;11(11):1080-3. doi: 10.1111/j.1463-1326.2009.01076.x. Epub 2009 Sep 9.


Aim: The uptake of drugs from the blood into the renal tubular cells is a key determinant for renal secretion and may influence their systemic plasma concentrations and extrarenal effects. Metformin, used for treatment of type 2 diabetes, is taken up into renal tubular cells by the organic cation transporter 2 (OCT2). Because many patients with type 2 diabetes receiving metformin are concomitantly treated with beta-blockers, we tested whether beta-blockers can inhibit OCT2-mediated drug transport.

Method: Using Madin-Darby canine kidney II cells stably expressing the uptake transporter OCT2, we analysed whether the beta-blockers bisoprolol, carvedilol, metoprolol and propranolol inhibit the transport of OCT2 substrates 1-methyl-4-phenylpyridinium (MPP(+)) and metformin.

Results: Neither bisoprolol nor metoprolol significantly inhibited the uptake of MPP(+), whereas a significant inhibition was observed for carvedilol und propranolol (half maximal inhibitory concentration IC(50): 26.3 and 67.5 microM) respectively. Moreover, all beta-blockers significantly inhibited OCT2-mediated metformin uptake (IC(50) for bisoprolol: 2.4 microM, IC(50) for carvedilol: 2.3 microM, IC(50) for metoprolol: 50.2 microM and IC(50) for propranolol: 8.3 microM).

Conclusion: These in vitro results demonstrate that alterations of uptake transporter function by beta-blockers have to be considered as potential mechanisms underlying drug-drug interactions in the kidney.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-Antagonists / pharmacology*
  • Biological Transport / drug effects
  • Bisoprolol / pharmacology
  • Carbazoles / pharmacology
  • Carvedilol
  • Cell Line
  • Humans
  • Kidney / drug effects
  • Kidney / metabolism*
  • Metformin / metabolism*
  • Metoprolol / pharmacology
  • Organic Cation Transport Proteins / antagonists & inhibitors*
  • Organic Cation Transport Proteins / metabolism
  • Organic Cation Transporter 2
  • Propanolamines / pharmacology
  • Propranolol / pharmacology


  • Adrenergic beta-Antagonists
  • Carbazoles
  • Organic Cation Transport Proteins
  • Organic Cation Transporter 2
  • Propanolamines
  • SLC22A2 protein, human
  • Carvedilol
  • Metformin
  • Propranolol
  • Metoprolol
  • Bisoprolol