PMID- 35183887
OWN - NLM
STAT- MEDLINE
DCOM- 20220315
LR  - 20220531
IS  - 1873-264X (Electronic)
IS  - 0731-7085 (Linking)
VI  - 212
DP  - 2022 Apr 1
TI  - Tamsulosin alters the pharmacokinetics of metformin via inhibition of renal 
      multidrug and toxin extrusion protein 1 and organic cation transporter 2 in rats.
PG  - 114666
LID - S0731-7085(22)00087-5 [pii]
LID - 10.1016/j.jpba.2022.114666 [doi]
AB  - Among the endocrine and metabolic disorders, type-2 diabetes mellitus (T2DM) and 
      benign prostatic hyperplasia (BPH) are common progressive diseases related to 
      aging. Metformin and tamsulosin as the first-choice drug for patients with T2DM 
      and BPH, respectively, are often co-administered to male patients with T2DM and 
      BPH. However, whether concomitantly administering metformin and tamsulosin leads 
      to drug-drug interactions (DDIs) remains unclear. This study aimed to evaluate 
      the effect of tamsulosin on the pharmacokinetics of metformin and explore the 
      relevant underlying mechanism. The plasma, urine, and tissue concentrations of 
      metformin were analyzed using HPLC, and metformin cell uptake was analyzed using 
      LC-MS/MS. In addition, western blotting was used to investigate the expression of 
      Oct1, Oct2, and Mate1. As demonstrated by comparison with metformin alone, 
      tamsulosin significantly increased the area under concentration-time curves 
      (AUC(0-t)), the maximum plasma concentration (C(max)) and the decreased 24 h 
      cumulative urinary excretion of metformin after single or multiple-dose 
      administration in rats, as well as increased the kidney tissue concentration of 
      metformin after multiple-dose. In addition, tamsulosin treatment significantly 
      inhibited the expression of Mate1 and Oct2 in rat kidneys, but Oct1 and Mate1 did 
      not show a significant difference in the liver. Consistently, tamsulosin 
      inhibited OCT2 and MATE1 expressions and decreased metformin uptake in HEK293 
      cells. Notably, serum LCA level in the co-administration group was increased by 
      34% and 39% after multiple-dose (7 and 14 consecutive days, respectively) 
      administration compared to the metformin alone group. Altogether, our data 
      suggest that tamsulosin could increase systemic exposure and reduce excretion of 
      metformin via inhibiting Oct2 and Mate1-mediated transport cooperatively.
CI  - Copyright (c) 2022 Elsevier B.V. All rights reserved.
FAU - Saad, Abdulaziz Ahmed A
AU  - Saad AAA
AD  - School of Pharmacy, Lanzhou University, Lanzhou 730000, China.
FAU - Zhang, Fan
AU  - Zhang F
AD  - Department of Pharmacy, the First Hospital of Lanzhou University, Lanzhou 730000, 
      China.
FAU - Refat, Moath
AU  - Refat M
AD  - School of Pharmacy, Lanzhou University, Lanzhou 730000, China.
FAU - Mohammed, Eyad Abdulwhab H
AU  - Mohammed EAH
AD  - School of Pharmacy, Lanzhou University, Lanzhou 730000, China.
FAU - Zhang, Mingkang
AU  - Zhang M
AD  - School of Pharmacy, Lanzhou University, Lanzhou 730000, China.
FAU - Chen, Yuyue
AU  - Chen Y
AD  - Department of Pharmacy, the First Hospital of Lanzhou University, Lanzhou 730000, 
      China.
FAU - Al Hamyari, Bandar
AU  - Al Hamyari B
AD  - School of Pharmacy, Lanzhou University, Lanzhou 730000, China.
FAU - Alafifi, Jameel
AU  - Alafifi J
AD  - School of Pharmacy, Lanzhou University, Lanzhou 730000, China.
FAU - Wu, Xin'an
AU  - Wu X
AD  - Department of Pharmacy, the First Hospital of Lanzhou University, Lanzhou 730000, 
      China. Electronic address: wuxa@lzu.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20220216
PL  - England
TA  - J Pharm Biomed Anal
JT  - Journal of pharmaceutical and biomedical analysis
JID - 8309336
RN  - 0 (Organic Cation Transport Proteins)
RN  - 0 (Organic Cation Transporter 2)
RN  - 0 (Slc22a2 protein, rat)
RN  - 9100L32L2N (Metformin)
RN  - G3P28OML5I (Tamsulosin)
SB  - IM
MH  - Animals
MH  - Chromatography, Liquid
MH  - HEK293 Cells
MH  - Humans
MH  - Kidney/metabolism
MH  - Male
MH  - *Metformin
MH  - Organic Cation Transport Proteins/metabolism/pharmacology
MH  - Organic Cation Transporter 2/metabolism
MH  - Rats
MH  - Tamsulosin/pharmacology
MH  - Tandem Mass Spectrometry
OTO - NOTNLM
OT  - Metformin
OT  - Multidrug and toxin extrusion 1
OT  - Organic cation transporter 2
OT  - Pharmacokinetic interaction
OT  - Tamsulosin
EDAT- 2022/02/21 06:00
MHDA- 2022/03/16 06:00
CRDT- 2022/02/20 20:33
PHST- 2021/11/17 00:00 [received]
PHST- 2022/01/30 00:00 [revised]
PHST- 2022/02/13 00:00 [accepted]
PHST- 2022/02/21 06:00 [pubmed]
PHST- 2022/03/16 06:00 [medline]
PHST- 2022/02/20 20:33 [entrez]
AID - S0731-7085(22)00087-5 [pii]
AID - 10.1016/j.jpba.2022.114666 [doi]
PST - ppublish
SO  - J Pharm Biomed Anal. 2022 Apr 1;212:114666. doi: 10.1016/j.jpba.2022.114666. Epub 
      2022 Feb 16.