Details of Drug Interaction

Details of Drug-Drug Interaction

 Drug General Information (ID: DDI26IGTRX)
  Drug Name Phenytoin Drug Info Sulfinpyrazone Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Anticonvulsants Uricosuric Agents
  Structure

 Mechanism of Phenytoin-Sulfinpyrazone Interaction (Severity Level: Moderate)
     Competitive binding of plasma proteins Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Phenytoin Sulfinpyrazone
      Mechanism 1 Competition for plasma protein binding sites Competition for plasma protein binding sites
      Key Mechanism Factor 1
Factor Name Plasma protein binding
Factor Description Plasma protein binding refers to the degree of binding of a drug to proteins in the blood, and the lower the degree of binding, the more efficiently the drug can cross cell membranes or diffuse. Plasma protein binding alters the distribution and therapeutic characteristics of the drugs.
      Mechanism Description
  • Increased plasma concentration of Sulfinpyrazone and Phenytoin due to competitive binding of plasma proteins
     CYP450 enzyme inhibition Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Phenytoin Sulfinpyrazone
      Mechanism 2 CYP450 2C9 substrate CYP450 2C9 inhibitor
      Key Mechanism Factor 2
Factor Name Cytochrome P450 2C9
×
Structure Sequence
MDSLVVLVLCLSCLLLLSLWRQSSGRGKLPPGPTPLPVIGNILQIGIKDISKSLTNLSKVYGPVFTLYFGLKPIVVLHGYEAVKEALIDLGEEFSGRGIFPLAERANRGFGIVFSNGKKWKEIRRFSLMTLRNFGMGKRSIEDRVQEEARCLVEELRKTKASPCDPTFILGCAPCNVICSIIFHKRFDYKDQQFLNLMEKLNENIKILSSPWIQICNNFSPIIDYFPGTHNKLLKNVAFMKSYILEKVKEHQESMDMNNPQDFIDCFLMKMEKEKHNQPSEFTIESLENTAVDLFGAGTETTSTTLRYALLLLLKHPEVTAKVQEEIERVIGRNRSPCMQDRSHMPYTDAVVHEVQRYIDLLPTSLPHAVTCDIKFRNYLIPKGTTILISLTSVLHDNKEFPNPEMFDPHHFLDEGGNFKKSKYFMPFSAGKRICVGEALAGMELFLFLTSILQNFNLKSLVDPKNLDTTPVVNGFASVPPFYQLCFIPV
Gene Name CYP2C9
Uniprot ID CP2C9_HUMAN
KEGG Pathway hsa:1559
Protein Family Cytochrome P450 family
Protein Function
A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids and steroids (PubMed:7574697, PubMed:9866708, PubMed:9435160, PubMed:12865317, PubMed:15766564, PubMed:19965576, PubMed:21576599). 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:9866708, PubMed:9435160, PubMed:12865317, PubMed:15766564, PubMed:19965576, PubMed:21576599). Catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) (PubMed:7574697, PubMed:15766564, PubMed:19965576, PubMed:9866708). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). Exhibits low catalytic activity for the formation of catechol estrogens from 17beta-estradiol (E2) and estrone (E1), namely 2-hydroxy E1 and E2 (PubMed:12865317). Catalyzes bisallylic hydroxylation and hydroxylation with double-bond migration of polyunsaturated fatty acids (PUFA) (PubMed:9866708, PubMed:9435160). Also metabolizes plant monoterpenes such as limonene. Oxygenates (R)- and (S)-limonene to produce carveol and perillyl alcohol (PubMed:11950794). Contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenytoin, tolbutamide and losartan (PubMed:25994031).
    Click to Show/Hide
      Mechanism Description
  • Decreased metabolism of Phenytoin caused by Sulfinpyrazone mediated inhibition of CYP450 enzyme

Recommended Action
      Management Caution is advised if sulfinpyrazone is used concomitantly with phenytoin. Dosage adjustments as well as clinical and laboratory monitoring should be considered whenever sulfinpyrazone is added to or withdrawn from therapy. Patients should be monitored for the development of phenytoin toxicity such as nausea, vomiting, tremors, ataxia, seizures, drowsiness, lethargy, slurred speech, visual disturbances, and changes in mental status.

References
1 Cerner Multum, Inc. "UK Summary of Product Characteristics.".
2 Pedersen AK, Jakobsen P, Kampmann JP, Hansen JM "Clinical pharmacokinetics and potentially important drug interactions of sulphinpyrazone." Clin Pharmacokinet 7 (1982): 42-56. [PMID: 7042172]