Drug General Information (ID: DDI6UHTZCM)
  Drug Name Cidofovir Drug Info Sacubitril Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Anti-Hiv Agents Neprilysin Inhibitors
  Structure

 Mechanism of Cidofovir-Sacubitril Interaction (Severity Level: Moderate)
     Transporter inhibition Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Cidofovir Sacubitril
      Mechanism OAT1 inhibitor OAT1 substrate
      Key Mechanism Factor 1
Factor Name Solute carrier family 22 member 6
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Structure Sequence
MAFNDLLQQVGGVGRFQQIQVTLVVLPLLLMASHNTLQNFTAAIPTHHCRPPADANLSKNGGLEVWLPRDRQGQPESCLRFTSPQWGLPFLNGTEANGTGATEPCTDGWIYDNSTFPSTIVTEWDLVCSHRALRQLAQSLYMVGVLLGAMVFGYLADRLGRRKVLILNYLQTAVSGTCAAFAPNFPIYCAFRLLSGMALAGISLNCMTLNVEWMPIHTRACVGTLIGYVYSLGQFLLAGVAYAVPHWRHLQLLVSAPFFAFFIYSWFFIESARWHSSSGRLDLTLRALQRVARINGKREEGAKLSMEVLRASLQKELTMGKGQASAMELLRCPTLRHLFLCLSMLWFATSFAYYGLVMDLQGFGVSIYLIQVIFGAVDLPAKLVGFLVINSLGRRPAQMAALLLAGICILLNGVIPQDQSIVRTSLAVLGKGCLAASFNCIFLYTGELYPTMIRQTGMGMGSTMARVGSIVSPLVSMTAELYPSMPLFIYGAVPVAASAVTVLLPETLGQPLPDTVQDLESRWAPTQKEAGIYPRKGKQTRQQQEHQKYMVPLQASAQEKNGL
Gene Name OAT1
Uniprot ID S22A6_HUMAN
KEGG Pathway hsa:9356
Protein Family Major facilitator (TC 2.A.1) superfamily
Protein Function
Involved in the renal elimination of endogenous and exogenous organic anions. Functions as organic anion exchanger when the uptake of one molecule of organic anion is coupled with an efflux of one molecule of endogenous dicarboxylic acid (glutarate, ketoglutarate, etc). Mediates the sodium-independent uptake of 2,3-dimercapto-1-propanesulfonic acid (DMPS) (By similarity). Mediates the sodium-independent uptake of p-aminohippurate (PAH), ochratoxin (OTA), acyclovir (ACV), 3'-azido-3-'deoxythymidine (AZT), cimetidine (CMD), 2,4-dichloro-phenoxyacetate (2,4-D), hippurate (HA), indoleacetate (IA), indoxyl sulfate (IS) and 3-carboxy-4-methyl-5-propyl-2-furanpropionate (CMPF), cidofovir, adefovir, 9-(2-phosphonylmethoxyethyl) guanine (PMEG), 9-(2-phosphonylmethoxyethyl) diaminopurine (PMEDAP) and edaravone sulfate. PAH uptake is inhibited by p-chloromercuribenzenesulphonate (PCMBS), diethyl pyrocarbonate (DEPC), sulindac, diclofenac, carprofen, glutarate and okadaic acid (By similarity). PAH uptake is inhibited by benzothiazolylcysteine (BTC), S-chlorotrifluoroethylcysteine (CTFC), cysteine S-conjugates S-dichlorovinylcysteine (DCVC), furosemide, steviol, phorbol 12-myristate 13-acetate (PMA), calcium ionophore A23187, benzylpenicillin, furosemide, indomethacin, bumetamide, losartan, probenecid, phenol red, urate, and alpha-ketoglutarate.
    Click to Show/Hide
      Mechanism Description
  • Decreased clearance of Sacubitril due to the transporter inhibition by Cidofovir 

Recommended Action
      Management Caution is advised if sacubitril is used in combination with inhibitors of OATP1B1, OATP1B3, OAT1, or OAT3. Pharmacologic response and blood pressure should be monitored more closely following the addition, discontinuation, or change of dosage of the transporter inhibitor, and the sacubitril dosage adjusted as necessary.

References
1 Cerner Multum, Inc. "Australian Product Information.".
2 Product Information. Nexletol (bempedoic acid). Esperion Therapeutics, Ann Arbor, MI.
3 Product Information. Nexlizet (bempedoic acid-ezetimibe). Esperion Therapeutics, Ann Arbor, MI.