PMID- 25486332
OWN - NLM
STAT- MEDLINE
DCOM- 20150917
LR  - 20200311
IS  - 1879-0720 (Electronic)
IS  - 0928-0987 (Linking)
VI  - 68
DP  - 2015 Feb 20
TI  - Inhibitory effect of atenolol on urinary excretion of metformin via 
      down-regulating multidrug and toxin extrusion protein 1 (rMate1) expression in 
      the kidney of rats.
PG  - 18-26
LID - S0928-0987(14)00441-2 [pii]
LID - 10.1016/j.ejps.2014.12.002 [doi]
AB  - Renal tubular secretion is an important pathway for the elimination of many 
      clinically used drugs. Metformin, a commonly prescribed first-line antidiabetic 
      drug, is secreted primarily by the renal tubule. Many patients with type 2 
      diabetes mellitus (T2DM) receiving metformin may together be given selective beta1 
      blockers (e.g., atenolol). Therefore, it is of great use to evaluate the effect 
      of atenolol on metformin urinary excretion for exploring drug interactions and 
      predicting the adverse effect of drugs. The aim of this study was to investigate 
      the effect of atenolol on the pharmacokinetic of metformin and plasma lactate 
      (LCA) level in rats, for high LCA is a serious adverse reaction of metformin 
      after long-term metformin treatment. In this study, rats were treated with 
      metformin alone or in combination with atenolol. Plasma, urine and tissue 
      concentration of metformin was determined by HPLC method, while Western blotting 
      and immunohistochemical analysis were used to evaluate the renal expression of 
      rat organic cation transporter 2 (rOct2) and multidrug and toxin extrusion 
      protein 1 (rMate1). The results showed that, after 7 days drug treatment, the 
      AUC0 --> t of metformin in atenolol and metformin co-administration group was 
      significantly increased by 19.5% compared to that in metformin group, while the 
      24h cumulative urinary excretion of metformin was significantly decreased by 
      57.3%. In addition, atenolol treatment significantly decreased the renal 
      expression of rMate1, but had no effect on rOct2 expression, renal blood 
      perfusion and glomerular filtration. Moreover, plasma LCA level in atenolol and 
      metformin co-administration group was significantly increased by 83.3% compared 
      to that in metformin group after 60 days drug treatment. These results indicated 
      that atenolol can inhibit urinary excretion of metformin via decreasing renal 
      rMate1 expression, and long-term atenolol and metformin co-administration may 
      induce potential lactic acidosis. Our results, for the first time, provided an 
      important experimental evidence that rMate1 is the target of transporter-mediated 
      drug interactions concerning metformin and atenolol.
CI  - Copyright (c) 2014 Elsevier B.V. All rights reserved.
FAU - Ma, Yan-rong
AU  - Ma YR
AD  - Department of Pharmacy, the First Hospital of Lanzhou University, Lanzhou 730000, 
      China; School of Pharmacy, Lanzhou University, Lanzhou 730000, China.
FAU - Huang, Jing
AU  - Huang J
AD  - Department of Pharmacy, the First Hospital of Lanzhou University, Lanzhou 730000, 
      China; School of Pharmacy, Lanzhou University, Lanzhou 730000, China.
FAU - Shao, Yun-yun
AU  - Shao YY
AD  - Department of Pharmacy, the First Hospital of Lanzhou University, Lanzhou 730000, 
      China; School of Pharmacy, Lanzhou University, Lanzhou 730000, China.
FAU - Ma, Kang
AU  - Ma K
AD  - Department of Pharmacy, the First Hospital of Lanzhou University, Lanzhou 730000, 
      China; School of Pharmacy, Lanzhou University, Lanzhou 730000, China.
FAU - Zhang, Guo-qiang
AU  - Zhang GQ
AD  - Department of Pharmacy, the First Hospital of Lanzhou University, Lanzhou 730000, 
      China.
FAU - Zhou, Yan
AU  - Zhou Y
AD  - Department of Pharmacy, the First Hospital of Lanzhou University, Lanzhou 730000, 
      China.
FAU - Zhi, Rao
AU  - Zhi R
AD  - Department of Pharmacy, the First Hospital of Lanzhou University, Lanzhou 730000, 
      China.
FAU - Qin, Hong-yan
AU  - Qin HY
AD  - Department of Pharmacy, the First Hospital of Lanzhou University, Lanzhou 730000, 
      China.
FAU - Wu, Xin-an
AU  - Wu XA
AD  - Department of Pharmacy, the First Hospital of Lanzhou University, Lanzhou 730000, 
      China. Electronic address: xinanwu6511@163.com.
LA  - eng
PT  - Journal Article
DEP - 20141205
PL  - Netherlands
TA  - Eur J Pharm Sci
JT  - European journal of pharmaceutical sciences : official journal of the European 
      Federation for Pharmaceutical Sciences
JID - 9317982
RN  - 0 (Adrenergic beta-1 Receptor Antagonists)
RN  - 0 (Antiporters)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Organic Cation Transport Proteins)
RN  - 0 (Organic Cation Transporter 2)
RN  - 0 (Slc22a2 protein, rat)
RN  - 0 (Slc47a1 protein, rat)
RN  - 50VV3VW0TI (Atenolol)
RN  - 9100L32L2N (Metformin)
SB  - IM
MH  - Adrenergic beta-1 Receptor Antagonists/*pharmacology
MH  - Animals
MH  - Antiporters/*metabolism
MH  - Atenolol/*pharmacology
MH  - Down-Regulation
MH  - Drug Interactions
MH  - Glomerular Filtration Rate/drug effects
MH  - Hypoglycemic Agents/blood/*pharmacokinetics/urine
MH  - Kidney/blood supply/*drug effects/metabolism/physiology
MH  - Liver/metabolism
MH  - Male
MH  - Metformin/blood/*pharmacokinetics/urine
MH  - Organic Cation Transport Proteins/*metabolism
MH  - Organic Cation Transporter 2
MH  - Rats, Wistar
MH  - Renal Circulation/drug effects
MH  - Tissue Distribution
OTO - NOTNLM
OT  - Atenolol
OT  - Metformin
OT  - Urinary excretion
OT  - rMate1
OT  - rOct2
EDAT- 2014/12/09 06:00
MHDA- 2015/09/18 06:00
CRDT- 2014/12/09 06:00
PHST- 2014/05/20 00:00 [received]
PHST- 2014/10/10 00:00 [revised]
PHST- 2014/12/01 00:00 [accepted]
PHST- 2014/12/09 06:00 [entrez]
PHST- 2014/12/09 06:00 [pubmed]
PHST- 2015/09/18 06:00 [medline]
AID - S0928-0987(14)00441-2 [pii]
AID - 10.1016/j.ejps.2014.12.002 [doi]
PST - ppublish
SO  - Eur J Pharm Sci. 2015 Feb 20;68:18-26. doi: 10.1016/j.ejps.2014.12.002. Epub 2014 
      Dec 5.