Drug General Information (ID: DDIS4ANZGP)
  Drug Name Esomeprazole Drug Info Stiripentol Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Antiulcer Agents Gamma-Aminobutyric Acid Reuptake Inhibitors
  Structure

 Mechanism of Esomeprazole-Stiripentol Interaction (Severity Level: Moderate)
     CYP450 enzyme inhibition Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Esomeprazole Stiripentol
      Mechanism CYP450 2C19 inhibitor CYP450 2C19 substrate
      Key Mechanism Factor 1
Factor Name Cytochrome P450 2C19
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Structure Sequence
MDPFVVLVLCLSCLLLLSIWRQSSGRGKLPPGPTPLPVIGNILQIDIKDVSKSLTNLSKIYGPVFTLYFGLERMVVLHGYEVVKEALIDLGEEFSGRGHFPLAERANRGFGIVFSNGKRWKEIRRFSLMTLRNFGMGKRSIEDRVQEEARCLVEELRKTKASPCDPTFILGCAPCNVICSIIFQKRFDYKDQQFLNLMEKLNENIRIVSTPWIQICNNFPTIIDYFPGTHNKLLKNLAFMESDILEKVKEHQESMDINNPRDFIDCFLIKMEKEKQNQQSEFTIENLVITAADLLGAGTETTSTTLRYALLLLLKHPEVTAKVQEEIERVIGRNRSPCMQDRGHMPYTDAVVHEVQRYIDLIPTSLPHAVTCDVKFRNYLIPKGTTILTSLTSVLHDNKEFPNPEMFDPRHFLDEGGNFKKSNYFMPFSAGKRICVGEGLARMELFLFLTFILQNFNLKSLIDPKDLDTTPVVNGFASVPPFYQLCFIPV
Gene Name CYP2C19
Uniprot ID CP2CJ_HUMAN
KEGG Pathway hsa:1557
Protein Family Cytochrome P450 family
Protein Function
A cytochrome P450 monooxygenase involved in the metabolism of polyunsaturated fatty acids (PUFA) (PubMed:18577768, PubMed:19965576, PubMed:20972997). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:18577768, PubMed:19965576, PubMed:20972997). Catalyzes the hydroxylation of carbon-hydrogen bonds. Hydroxylates PUFA specifically at the omega-1 position (PubMed:18577768). Catalyzes the epoxidation of double bonds of PUFA (PubMed:20972997, PubMed:19965576). Also metabolizes plant monoterpenes such as limonene. Oxygenates (R)- and (S)-limonene to produce carveol and perillyl alcohol (PubMed:11950794). Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine. Hydroxylates fenbendazole at the 4' position (PubMed:23959307).
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      Mechanism Description
  • Decreased metabolism of Stiripentol caused by Esomeprazole mediated inhibition of CYP450 enzyme

Recommended Action
      Management Caution is advised when stiripentol is used with CYP450 1A2, 2C19, and/or 3A4 inhibitors. Patients should be monitored for potentially increased adverse effects such as anorexia, nausea, vomiting, weight loss, somnolence, dizziness, confusion, difficulty concentrating, ataxia, hypotonia, tremor, hyperkinesia, dysarthria, suicidal ideation/behaviour, neutropenia, and thrombocytopenia. Dosage adjustments for stiripentol or alternative treatments may be required if an interaction is suspected.

References
1 Cerner Multum, Inc. "UK Summary of Product Characteristics.".
2 EMEA. European Medicines Agency "EPARs. European Union Public Assessment Reports.".
3 Product Information. Diacomit (stiripentol). Biocodex Inc, Creswell, OR.