Details of Drug Interaction

Details of Drug-Drug Interaction

 Drug General Information (ID: DDIQK9CMHI)
  Drug Name Gemfibrozil Drug Info Dasabuvir Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Antihyperammonia Agents Antiviral Agents
  Structure

 Mechanism of Gemfibrozil-Dasabuvir Interaction (Severity Level: Major)
     CYP450 enzyme inhibition Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Gemfibrozil Dasabuvir
      Mechanism CYP450 2C8 inhibitor CYP450 2C8 substrate
      Key Mechanism Factor 1
Factor Name Cytochrome P450 2C8
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Structure Sequence
MEPFVVLVLCLSFMLLFSLWRQSCRRRKLPPGPTPLPIIGNMLQIDVKDICKSFTNFSKVYGPVFTVYFGMNPIVVFHGYEAVKEALIDNGEEFSGRGNSPISQRITKGLGIISSNGKRWKEIRRFSLTTLRNFGMGKRSIEDRVQEEAHCLVEELRKTKASPCDPTFILGCAPCNVICSVVFQKRFDYKDQNFLTLMKRFNENFRILNSPWIQVCNNFPLLIDCFPGTHNKVLKNVALTRSYIREKVKEHQASLDVNNPRDFIDCFLIKMEQEKDNQKSEFNIENLVGTVADLFVAGTETTSTTLRYGLLLLLKHPEVTAKVQEEIDHVIGRHRSPCMQDRSHMPYTDAVVHEIQRYSDLVPTGVPHAVTTDTKFRNYLIPKGTTIMALLTSVLHDDKEFPNPNIFDPGHFLDKNGNFKKSDYFMPFSAGKRICAGEGLARMELFLFLTTILQNFNLKSVDDLKNLNTTAVTKGIVSLPPSYQICFIPV
Gene Name CYP2C8
Uniprot ID CP2C8_HUMAN
KEGG Pathway hsa:1558
Protein Family Cytochrome P450 family
Protein Function
A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids, steroid hormones and vitamins (PubMed:7574697, PubMed:11093772, PubMed:14559847, PubMed:15766564, PubMed:19965576). 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:7574697, PubMed:11093772, PubMed:14559847, PubMed:15766564, PubMed:19965576). Primarily catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) with a preference for the last double bond (PubMed:7574697, PubMed:15766564, PubMed:19965576). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes all trans-retinoic acid toward its 4-hydroxylated form (PubMed:11093772). Displays 16-alpha hydroxylase activity toward estrogen steroid hormones, 17beta-estradiol (E2) and estrone (E1) (PubMed:14559847). Plays a role in the oxidative metabolism of xenobiotics. It is the principal enzyme responsible for the metabolism of the anti-cancer drug paclitaxel (taxol) (PubMed:26427316).
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      Mechanism Description
  • Decreased metabolism of Dasabuvir caused by Gemfibrozil mediated inhibition of CYP450 enzyme

Recommended Action
      Management Concomitant use of dasabuvir with potent CYP450 2C8 inhibitors is considered contraindicated.

References
1 Ogilvie BW, Zhang D, Li W, et al. "Glucuronidation converts gemfibrozil to a potent, metabolism-dependent inhibitor of CYP2C8: implications for drug-drug interactions." Drug Metab Dispos 34 (2006): 191-7. [PMID: 16299161]
2 Product Information. Viekira Pak (dasabuvir/ombitasvir/paritaprevir/ritonavir). AbbVie US LLC, North Chicago, IL.
3 Tornio A, Filppula A, Kailari O, et al. "Glucuronidation converts clopidogrel to a strong time-dependent inhibitor of CYP2C8: a phase II metabolite as perpetrator of drug-drug interactions." Clin Pharmacol Ther 96 (2014): 498-507. [PMID: 24971633]