Details of Drug Interaction

Details of Drug-Drug Interaction

 Drug General Information (ID: DDICTDLEIS)
  Drug Name Metformin Drug Info Pexidartinib Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Antidiabetic Agents Multikinase Inhibitors
  Structure

 Mechanism of Metformin-Pexidartinib Interaction (Severity Level: Moderate)
     Transporter inhibition Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Metformin Pexidartinib
      Mechanism 1 MATE1 substrate MATE1 inhibitor
      Key Mechanism Factor 1
Factor Name Solute carrier family 47 member 1
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Structure Sequence
MEAPEEPAPVRGGPEATLEVRGSRCLRLSAFREELRALLVLAGPAFLVQLMVFLISFISSVFCGHLGKLELDAVTLAIAVINVTGVSVGFGLSSACDTLISQTYGSQNLKHVGVILQRSALVLLLCCFPCWALFLNTQHILLLFRQDPDVSRLTQTYVTIFIPALPATFLYMLQVKYLLNQGIVLPQIVTGVAANLVNALANYLFLHQLHLGVIGSALANLISQYTLALLLFLYILGKKLHQATWGGWSLECLQDWASFLRLAIPSMLMLCMEWWAYEVGSFLSGILGMVELGAQSIVYELAIIVYMVPAGFSVAASVRVGNALGAGDMEQARKSSTVSLLITVLFAVAFSVLLLSCKDHVGYIFTTDRDIINLVAQVVPIYAVSHLFEALACTSGGVLRGSGNQKVGAIVNTIGYYVVGLPIGIALMFATTLGVMGLWSGIIICTVFQAVCFLGFIIQLNWKKACQQAQVHANLKVNNVPRSGNSALPQDPLHPGCPENLEGILTNDVGKTGEPQSDQQMRQEEPLPEHPQDGAKLSRKQLVLRRGLLLLGVFLILLVGILVRFYVRIQ
Gene Name MATE1
Uniprot ID S47A1_HUMAN
KEGG Pathway hsa:55244
Protein Family Multi antimicrobial extrusion (MATE) (TC 2.A.66.1) family
Protein Function
Solute transporter for tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP), cimetidine, N-methylnicotinamide (NMN), metformin, creatinine, guanidine, procainamide, topotecan, estrone sulfate, acyclovir, ganciclovir and also the zwitterionic cephalosporin, cephalexin and cephradin. Seems to also play a role in the uptake of oxaliplatin (a new platinum anticancer agent). Able to transport paraquat (PQ or N,N-dimethyl-4-4'-bipiridinium); a widely used herbicid. Responsible for the secretion of cationic drugs across the brush border membranes.
    Click to Show/Hide
      Mechanism Description
  • Decreased clearance of Metformin due to the transporter inhibition by Pexidartinib 
      Mechanism 2 MATE2K substrate MATE2K inhibitor
      Key Mechanism Factor 2
Factor Name Multidrug and toxin extrusion protein 2
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Structure Sequence
MDSLQDTVALDHGGCCPALSRLVPRGFGTEMWTLFALSGPLFLFQVLTFMIYIVSTVFCGHLGKVELASVTLAVAFVNVCGVSVGVGLSSACDTLMSQSFGSPNKKHVGVILQRGALVLLLCCLPCWALFLNTQHILLLFRQDPDVSRLTQDYVMIFIPGLPVIFLYNLLAKYLQNQGWLKGQEEESPFQTPGLSILHPSHSHLSRASFHLFQKITWPQVLSGVVGNCVNGVANYALVSVLNLGVRGSAYANIISQFAQTVFLLLYIVLKKLHLETWAGWSSQCLQDWGPFFSLAVPSMLMICVEWWAYEIGSFLMGLLSVVDLSAQAVIYEVATVTYMIPLGLSIGVCVRVGMALGAADTVQAKRSAVSGVLSIVGISLVLGTLISILKNQLGHIFTNDEDVIALVSQVLPVYSVFHVFEAICCVYGGVLRGTGKQAFGAAVNAITYYIIGLPLGILLTFVVRMRIMGLWLGMLACVFLATAAFVAYTARLDWKLAAEEAKKHSGRQQQQRAESTATRPGPEKAVLSSVATGSSPGITLTTYSRSECHVDFFRTPEEAHALSAPTSRLSVKQLVIRRGAALGAASATLMVGLTVRILATRH
Gene Name MATE2
Uniprot ID S47A2_HUMAN
KEGG Pathway hsa:146802
Protein Family Multi antimicrobial extrusion (MATE) (TC 2.A.66.1) family
Protein Function
Solute transporter for tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP), cimetidine, N-methylnicotinamide, metformin, creatinine, guanidine, procainamide, topotecan, estrone sulfate, acyclovir, and ganciclovir. Responsible for the secretion of cationic drugs across the brush border membranes.
    Click to Show/Hide
      Mechanism Description
  • Decreased clearance of Metformin due to the transporter inhibition by Pexidartinib 

Recommended Action
      Management Caution is advised if pexidartinib is used concomitantly with drugs that are substrates of MATE1, MATE2K, OATP1B1, OATP1B3, and OATP2B1, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring should be considered whenever pexidartinib is added to or withdrawn from therapy with these drugs. Patients should be monitored for the development of adverse effects.

References
1 Product Information. Olysio (simeprevir). Janssen Pharmaceuticals, Titusville, NJ.
2 Product Information. Turalio (pexidartinib). Daiichi Sankyo, Inc., Parsippany, NJ.