Details of Drug Interaction

Details of Drug-Drug Interaction

 Drug General Information (ID: DDINZTAXQL)
  Drug Name Duloxetine Drug Info Echinacea Drug Info
  Drug Type Small molecule Natural product
  Therapeutic Class Antidepressants Herbal Products

 Mechanism of Duloxetine-Echinacea Interaction (Severity Level: Moderate)
     CYP450 enzyme inhibition Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Duloxetine Echinacea
      Mechanism CYP450 1A2 substrate CYP450 1A2 inhibitor
      Key Mechanism Factor 1
Factor Name Cytochrome P450 1A2
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Structure Sequence
MALSQSVPFSATELLLASAIFCLVFWVLKGLRPRVPKGLKSPPEPWGWPLLGHVLTLGKNPHLALSRMSQRYGDVLQIRIGSTPVLVLSRLDTIRQALVRQGDDFKGRPDLYTSTLITDGQSLTFSTDSGPVWAARRRLAQNALNTFSIASDPASSSSCYLEEHVSKEAKALISRLQELMAGPGHFDPYNQVVVSVANVIGAMCFGQHFPESSDEMLSLVKNTHEFVETASSGNPLDFFPILRYLPNPALQRFKAFNQRFLWFLQKTVQEHYQDFDKNSVRDITGALFKHSKKGPRASGNLIPQEKIVNLVNDIFGAGFDTVTTAISWSLMYLVTKPEIQRKIQKELDTVIGRERRPRLSDRPQLPYLEAFILETFRHSSFLPFTIPHSTTRDTTLNGFYIPKKCCVFVNQWQVNHDPELWEDPSEFRPERFLTADGTAINKPLSEKMMLFGMGKRRCIGEVLAKWEIFLFLAILLQQLEFSVPPGVKVDLTPIYGLTMKHARCEHVQARLRFSIN
Gene Name CYP1A2
Uniprot ID CP1A2_HUMAN
KEGG Pathway hsa:1544
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:9435160, PubMed:10681376, PubMed:11555828, PubMed:12865317, 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:9435160, PubMed:10681376, PubMed:11555828, PubMed:12865317, PubMed:19965576). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:11555828, PubMed:12865317). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2 (PubMed:11555828, PubMed:12865317). Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). May act as a major enzyme for all-trans retinoic acid biosynthesis in the liver. Catalyzes two successive oxidative transformation of all-trans retinol to all-trans retinal and then to the active form all-trans retinoic acid (PubMed:10681376). Primarily catalyzes stereoselective epoxidation of the last double bond of polyunsaturated fatty acids (PUFA), displaying a strong preference for the (R,S) stereoisomer (PubMed:19965576). Catalyzes bisallylic hydroxylation and omega-1 hydroxylation of PUFA (PubMed:9435160). May also participate in eicosanoids metabolism by converting hydroperoxide species into oxo metabolites (lipoxygenase-like reaction, NADPH-independent) (PubMed:21068195). Plays a role in the oxidative metabolism of xenobiotics. Catalyzes the N-hydroxylation of heterocyclic amines and the O-deethylation of phenacetin (PubMed:14725854). Metabolizes caffeine via N3-demethylation (Probable).
    Click to Show/Hide
      Mechanism Description
  • Decreased metabolism of Duloxetine caused by Echinacea mediated inhibition of CYP450 enzyme

Recommended Action
      Management Caution is advised if duloxetine is used in combination with CYP450 1A2 inhibitors. Pharmacologic response to duloxetine should be monitored more closely whenever a CYP450 1A2 inhibitor is added to or withdrawn from therapy, and the dosage adjusted as necessary.

References
1 Brosen K, Skjelbo E, Rasmussen BB, Poulsen HE, Loft S "Fluvoxamine is a potent inhibitor of cytochrome P4501A2." Biochem Pharmacol 45 (1993): 1211-4. [PMID: 8466541]
2 Martinez C, Albet C, Agundez JA, et al. "Comparative in vitro and in vivo inhibition of cytochrome P450 CYP1A2, CYP2D6, and CYP3A by H2-receptor antagonists." Clin Pharmacol Ther 65 (1999): 369-76. [PMID: 10223772]
3 Product Information. Cymbalta (duloxetine). Lilly, Eli and Company, Indianapolis, IN.
4 Uwe F, Strobl G, Manaut F, et al "Quinolone antibacterial agents: relationship between structure and in vitro inhibition of the human cytochrome P450 isofaorm CYP1A2." Mol Pharmacol 43 (1993): 191-9. [PMID: 8429824]