Details of Drug Interaction | MecDDI

Drug General Information (ID: DDIPTRM49K)
Drug Name			Enoxacin		Drug Info		Aminophylline		Drug Info
Drug Type		Small molecule				Small molecule
Therapeutic Class		Antiinfective Agents				Bronchodilators
Structure

Mechanism of Enoxacin-Aminophylline Interaction (Severity Level: Major)
CYP450 enzyme inhibition Click to Show/Hide Mechanism Graph

Drug Name		Enoxacin				Aminophylline
Mechanism		CYP450 1A2 inhibitor				CYP450 1A2 substrate
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		Decreased metabolism of Aminophylline caused by Enoxacin mediated inhibition of CYP450 enzyme

Recommended Action
Management		If possible, enoxacin therapy should be avoided in patients receiving theophylline. Levofloxacin, sparfloxacin, moxifloxacin, gatifloxacin, trovafloxacin, and lomefloxacin have been reported to cause minor or no changes in theophylline levels and may be considered as alternatives. If enoxacin is given concomitantly with theophylline, the theophylline dosage should be reduced approximately 50% or more, and theophylline serum levels should be closely monitored. Patients should be advised to report any signs of theophylline toxicity including nausea, vomiting, diarrhea, headache, restlessness, insomnia, seizures, or irregular heartbeats to their physician.

References
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2	Hardman JG, Gilman AG, Limbird LE eds. "Goodman and Gilman's the Pharmacological Basis of Therapeutics. 9th ed." New York, NY: McGraw-Hill (1995):.
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5	Rogge MC, Solomon WR, Sedman AJ, et al "The theophylline-enoxacin interaction. I: effect of enoxacin dose size on theophylline disposition." Clin Pharmacol Ther 44 (1988): 579-87. [PMID: 3180639]
6	Rogge MC, Solomon WR, Sedman AJ, et al "The theophylline-enoxacin interaction. II: Changes in the disposition of theophylline and its metabolites during intermittent administration of enoxacin." Clin Pharmacol Ther 46 (1989): 420-8. [PMID: 2791445]
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9	Sijnands WJ, Vree TB, Baars AM, Van Herwaarden CL "Steady-state kinetics of the quinolone derivatives ofloxacin, enoxacin, ciprofloxacin and pefloxacin during maintenance treatment with theopylline." Drugs 34 (1987): 159-69. [PMID: 3481317]
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17	Wijnands WJ, Vree TB, Baars AM, van Herwaarden CL "Steady-state kinetics of the quinolone derivatives ofloxacin, enoxacin, ciprofloxacin and pefloxacin during maintneance treatment with theophylline." Drugs 34 (1987): 159-69. [PMID: 3481317]
18	Wijnands WJ, Vree TB, van Herwaarden CL "Enoxacin decreases the clearance of theophylline in man." Br J Clin Pharmacol 20 (1985): 583-8. [PMID: 3867394]