Details of Drug Interaction

Details of Drug-Drug Interaction

 Drug General Information (ID: DDI7MF6JI9)
  Drug Name Nitisinone Drug Info Sitagliptin Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Antineoplastics Antidiabetic Agents
  Structure

 Mechanism of Nitisinone-Sitagliptin Interaction (Severity Level: Moderate)
     Transporter inhibition Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Nitisinone Sitagliptin
      Mechanism OAT3 inhibitor OAT3 substrate
      Key Mechanism Factor 1
Factor Name Solute carrier family 22 member 8
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Structure Sequence
MTFSEILDRVGSMGHFQFLHVAILGLPILNMANHNLLQIFTAATPVHHCRPPHNASTGPWVLPMGPNGKPERCLRFVHPPNASLPNDTQRAMEPCLDGWVYNSTKDSIVTEWDLVCNSNKLKEMAQSIFMAGILIGGLVLGDLSDRFGRRPILTCSYLLLAASGSGAAFSPTFPIYMVFRFLCGFGISGITLSTVILNVEWVPTRMRAIMSTALGYCYTFGQFILPGLAYAIPQWRWLQLTVSIPFFVFFLSSWWTPESIRWLVLSGKSSKALKILRRVAVFNGKKEEGERLSLEELKLNLQKEISLAKAKYTASDLFRIPMLRRMTFCLSLAWFATGFAYYSLAMGVEEFGVNLYILQIIFGGVDVPAKFITILSLSYLGRHTTQAAALLLAGGAILALTFVPLDLQTVRTVLAVFGKGCLSSSFSCLFLYTSELYPTVIRQTGMGVSNLWTRVGSMVSPLVKITGEVQPFIPNIIYGITALLGGSAALFLPETLNQPLPETIEDLENWSLRAKKPKQEPEVEKASQRIPLQPHGPGLGSS
Gene Name OAT3
Uniprot ID S22A8_HUMAN
KEGG Pathway hsa:9376
Protein Family Major facilitator (TC 2.A.1) superfamily
Protein Function
Plays an important role in the excretion/detoxification of endogenous and exogenous organic anions, especially from the brain and kidney. Involved in the transport basolateral of steviol, fexofenadine. Transports benzylpenicillin (PCG), estrone-3-sulfate (E1S), cimetidine (CMD), 2,4-dichloro-phenoxyacetate (2,4-D), p-amino-hippurate (PAH), acyclovir (ACV) and ochratoxin (OTA).
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      Mechanism Description
  • Decreased clearance of Sitagliptin due to the transporter inhibition by Nitisinone 

Recommended Action
      Management Caution is advised if nitisinone is used in combination with OAT1/OAT3 substrates. Patients should be monitored for potential adverse reactions related to increased plasma concentrations of the OAT1/OAT3 substrate.

References
1 Product Information. Orfadin (nitisinone). Orphan Pharmaceuticals USA, Inc, Nashville, TN.