Details of Drug Interaction

Details of Drug-Drug Interaction

 Drug General Information (ID: DDI3P4E0X6)
  Drug Name Theophylline Drug Info St. John's Wort Drug Info
  Drug Type Small molecule Natural product
  Therapeutic Class Bronchodilators Herbal Products/Antidepressants

 Mechanism of Theophylline-St. John's Wort Interaction (Severity Level: Moderate)
     CYP450 enzyme induction Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Theophylline St. John's Wort
      Mechanism CYP450 1A2 substrate CYP450 1A2 inducer
      Key Mechanism Factor 1
Factor Name Cytochrome P450 1A2
×
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
  • Increased metabolism of Theophylline caused by St. John's Wort mediated induction of CYP450 enzyme

Recommended Action
      Management Patients should consult a healthcare provider before taking any herbal or alternative medicine. Pharmacologic response and serum theophylline levels should be monitored more closely whenever St. John's wort is added to or withdrawn from therapy, and the methylxanthine dosage adjusted as necessary. Patients should be advised to notify their physician if they experience loss of asthma control or worsening of respiratory symptoms.

References
1 Fugh-Berman A "Herb-drug interactions." Lancet 355 (2000): 134-8. [PMID: 10675182]
2 Izzo AA, Ernst E "Interactions between herbal medicines and prescribed drugs: a systematic review." Drugs 61 (2001): 2163-75. [PMID: 11772128]
3 Nebel A, Schneider BJ, Baker RK, Kroll DJ "Potential metabolic interaction between St. John's wort and theophylline." Ann Pharmacother 33 (1999): 502. [PMID: 10332544]