Details of Drug Interaction

Details of Drug-Drug Interaction

 Drug General Information (ID: DDI2BZQECT)
  Drug Name Clobazam Drug Info Cimetidine Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Benzodiazepine Anticonvulsants Antiulcer Agents
  Structure

 Mechanism of Clobazam-Cimetidine Interaction (Severity Level: Moderate)
     CYP450 enzyme inhibition Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Clobazam Cimetidine
      Mechanism CYP450 2C19 substrate CYP450 2C19 inhibitor
      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 Clobazam caused by Cimetidine mediated inhibition of CYP450 enzyme

Recommended Action
      Management Caution is advised if clobazam is prescribed in combination with cimetidine. Available data seem to suggest that the magnitude of interaction may be minimized by separating the times of administration of cimetidine and clobazam by as much as possible.

References
1 Grigoleit HG, Hajdu P, Hundt HK, et al. "Pharmacokinetic aspects of the interaction between clobazam and cimetidine." Eur J Clin Pharmacol 25 (1983): 139-42. [PMID: 6617718]
2 Pullar T, Edwards D, Haigh JR, Peaker S, Feely MP "The effect of cimetidine on the single dose pharmacokinetics of oral clobazam and N-desmethylclobazam." Br J Clin Pharmacol 23 (1987): 317-21. [PMID: 3567046]