Details of the Drug Combination

General Information of Drug Combination (ID: DCABJX7)

Drug Combination Name
Phenytoin Valproic Acid
Indication
Disease Entry Status REF
Drug Resistant Epilepsy Phase 4 [1]
Component Drugs Phenytoin   DMNOKBV Valproic Acid   DMS49KH
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Phenytoin
Disease Entry ICD 11 Status REF
Epilepsy 8A60-8A68 Approved [2]
Epilepsy with generalized tonic-clonic seizures N.A. Approved [3]
Focal epilepsy N.A. Approved [3]
Primary motor cortex epilepsy N.A. Approved [3]
Phenytoin Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Sodium channel unspecific (NaC) TTRK8B9 NOUNIPROTAC Blocker [10]
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Phenytoin Interacts with 3 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
Multidrug resistance-associated protein 1 (ABCC1) DTSYQGK MRP1_HUMAN Substrate [11]
Multidrug resistance-associated protein 2 (ABCC2) DTFI42L MRP2_HUMAN Substrate [12]
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [13]
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Phenytoin Interacts with 9 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [14]
Glutathione S-transferase alpha-1 (GSTA1) DE4ZHS1 GSTA1_HUMAN Metabolism [15]
Cytochrome P450 3A5 (CYP3A5) DEIBDNY CP3A5_HUMAN Metabolism [16]
Cytochrome P450 3A7 (CYP3A7) DERD86B CP3A7_HUMAN Metabolism [16]
Cytochrome P450 2C18 (CYP2C18) DEZMWRE CP2CI_HUMAN Metabolism [17]
Cytochrome P450 2C8 (CYP2C8) DES5XRU CP2C8_HUMAN Metabolism [17]
Cytochrome P450 2C9 (CYP2C9) DE5IED8 CP2C9_HUMAN Metabolism [18]
Cytochrome P450 2B6 (CYP2B6) DEPKLMQ CP2B6_HUMAN Metabolism [16]
Mephenytoin 4-hydroxylase (CYP2C19) DEGTFWK CP2CJ_HUMAN Metabolism [17]
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⏷ Show the Full List of 9 DME(s)
Phenytoin Interacts with 122 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) OTQGYY83 CP3A4_HUMAN Increases Expression [19]
Glutathione S-transferase A1 (GSTA1) OTA7K5XA GSTA1_HUMAN Increases Expression [20]
Cytochrome P450 3A5 (CYP3A5) OTSXFBXB CP3A5_HUMAN Increases Expression [21]
Cytochrome P450 2B6 (CYP2B6) OTOYO4S7 CP2B6_HUMAN Increases Expression [22]
Cytochrome P450 3A7 (CYP3A7) OTTCDHHM CP3A7_HUMAN Increases Expression [21]
Cytochrome P450 2C19 (CYP2C19) OTFMJYYE CP2CJ_HUMAN Decreases Hydroxylation [23]
ATP-dependent translocase ABCB1 (ABCB1) OTEJROBO MDR1_HUMAN Increases Metabolism [24]
ATP-binding cassette sub-family C member 2 (ABCC2) OTJSIGV5 MRP2_HUMAN Affects Response To Substance [25]
HLA class I histocompatibility antigen, B alpha chain (HLA-B) OTNXFWY2 HLAB_HUMAN Affects Response To Substance [26]
HLA class I histocompatibility antigen, C alpha chain (HLA-C) OTV38BUJ HLAC_HUMAN Increases ADR [26]
HLA class I histocompatibility antigen, A alpha chain (HLA-A) OTAH14LU HLAA_HUMAN Increases ADR [26]
Cytochrome P450 1A1 (CYP1A1) OTE4EFH8 CP1A1_HUMAN Increases Expression [27]
Cellular tumor antigen p53 (TP53) OTIE1VH3 P53_HUMAN Increases Expression [20]
Nuclear receptor subfamily 1 group I member 2 (NR1I2) OTC5U0N5 NR1I2_HUMAN Increases Activity [28]
Aromatase (CYP19A1) OTZ6XF74 CP19A_HUMAN Decreases Activity [29]
Cytochrome P450 2E1 (CYP2E1) OTHQ17JG CP2E1_HUMAN Increases Expression [30]
Serum paraoxonase/arylesterase 1 (PON1) OTD0Z2XO PON1_HUMAN Affects Activity [31]
Neurocan core protein (NCAN) OT8OO6ZE NCAN_HUMAN Increases Expression [8]
Plexin-B2 (PLXNB2) OT56I2VD PLXB2_HUMAN Decreases Expression [8]
Calpain-5 (CAPN5) OTQ8QM7K CAN5_HUMAN Decreases Expression [8]
Leucine-rich repeat transmembrane protein FLRT2 (FLRT2) OTGD8TID FLRT2_HUMAN Increases Expression [8]
Fibroblast growth factor receptor substrate 3 (FRS3) OTTNP6H7 FRS3_HUMAN Decreases Expression [8]
Lathosterol oxidase (SC5D) OT41KMW4 SC5D_HUMAN Increases Expression [8]
Retinal dehydrogenase 2 (ALDH1A2) OTJB560Z AL1A2_HUMAN Decreases Expression [7]
Eomesodermin homolog (EOMES) OTB9VQFA EOMES_HUMAN Increases Expression [8]
Metalloproteinase inhibitor 1 (TIMP1) OTOXC51H TIMP1_HUMAN Increases Expression [32]
Myc proto-oncogene protein (MYC) OTPV5LUK MYC_HUMAN Increases Expression [33]
Platelet-derived growth factor subunit B (PDGFB) OTMFMFC3 PDGFB_HUMAN Increases Expression [8]
Parathyroid hormone (PTH) OTD721UF PTHY_HUMAN Increases Expression [34]
Tumor necrosis factor (TNF) OT4IE164 TNFA_HUMAN Increases Expression [8]
Collagen alpha-1(I) chain (COL1A1) OTI31178 CO1A1_HUMAN Decreases Expression [35]
Fibronectin (FN1) OTB5ZN4Q FINC_HUMAN Increases Expression [8]
Alpha-fetoprotein (AFP) OT9GG3ZI FETA_HUMAN Decreases Expression [8]
Interstitial collagenase (MMP1) OTI4I2V1 MMP1_HUMAN Decreases Expression [36]
Platelet-derived growth factor subunit A (PDGFA) OTCMZ0W8 PDGFA_HUMAN Increases Expression [8]
Integrin beta-1 (ITGB1) OT6G1IAR ITB1_HUMAN Decreases Expression [36]
Insulin receptor (INSR) OTTY341H INSR_HUMAN Increases Expression [8]
Creatine kinase M-type (CKM) OTME0KO7 KCRM_HUMAN Increases Expression [37]
Procathepsin L (CTSL) OTYTUW29 CATL1_HUMAN Increases Expression [32]
Cathepsin B (CTSB) OTP9G5QB CATB_HUMAN Increases Expression [8]
Collagen alpha-2(I) chain (COL1A2) OTY7G382 CO1A2_HUMAN Increases Expression [8]
Chymotrypsin-like elastase family member 2A (CELA2A) OTY8QG2J CEL2A_HUMAN Decreases Expression [8]
72 kDa type IV collagenase (MMP2) OT5NIWA2 MMP2_HUMAN Decreases Expression [36]
Stromelysin-1 (MMP3) OTGBI74Z MMP3_HUMAN Decreases Expression [36]
Small ribosomal subunit protein uS2 (RPSA) OTJZHEGT RSSA_HUMAN Increases Expression [8]
Annexin A4 (ANXA4) OTUCRYXL ANXA4_HUMAN Increases Expression [8]
Homeobox protein Hox-B7 (HOXB7) OTC7WYU8 HXB7_HUMAN Increases Expression [7]
Calmodulin-1 (CALM2) OTNYA92F CALM1_HUMAN Decreases Expression [8]
Transforming growth factor beta-3 proprotein (TGFB3) OT2LOUQ1 TGFB3_HUMAN Increases Expression [8]
Fibroblast growth factor 5 (FGF5) OTQXGHBY FGF5_HUMAN Increases Expression [8]
Collagen alpha-1(XI) chain (COL11A1) OTB0DRMS COBA1_HUMAN Increases Expression [8]
Collagen alpha-1(VI) chain (COL6A1) OTYKSCOB CO6A1_HUMAN Decreases Expression [8]
Collagen alpha-2(VI) chain (COL6A2) OTQC6PPO CO6A2_HUMAN Increases Expression [38]
Collagen alpha-3(VI) chain (COL6A3) OTAS6R6I CO6A3_HUMAN Increases Expression [38]
Bone morphogenetic protein 1 (BMP1) OTRFFAL4 BMP1_HUMAN Decreases Expression [8]
Interferon gamma receptor 1 (IFNGR1) OTCTQBWW INGR1_HUMAN Increases Expression [8]
Methylated-DNA--protein-cysteine methyltransferase (MGMT) OT40A9WH MGMT_HUMAN Increases Methylation [39]
Integrin alpha-2 (ITGA2) OTPFL017 ITA2_HUMAN Decreases Expression [36]
Homeobox protein Hox-B9 (HOXB9) OTMVHQOU HXB9_HUMAN Increases Expression [7]
Nuclear factor NF-kappa-B p105 subunit (NFKB1) OTNRRD8I NFKB1_HUMAN Increases Expression [8]
Midkine (MDK) OTF24HKC MK_HUMAN Increases Expression [8]
Fibroblast growth factor receptor 2 (FGFR2) OTLOPACK FGFR2_HUMAN Increases Expression [40]
Paired box protein Pax-3 (PAX3) OTN5PJZV PAX3_HUMAN Decreases Expression [7]
G1/S-specific cyclin-D1 (CCND1) OT8HPTKJ CCND1_HUMAN Decreases Expression [8]
NF-kappa-B inhibitor alpha (NFKBIA) OTFT924M IKBA_HUMAN Decreases Degradation [36]
Paired box protein Pax-6 (PAX6) OTOC9876 PAX6_HUMAN Increases Expression [7]
Protein S100-A4 (S100A4) OTLRGFSQ S10A4_HUMAN Increases Expression [8]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Decreases Phosphorylation [36]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Decreases Phosphorylation [36]
Fibroblast growth factor 9 (FGF9) OT2SKDGM FGF9_HUMAN Increases Expression [8]
Keratin, type II cytoskeletal 2 epidermal (KRT2) OTG2EZEN K22E_HUMAN Increases Expression [8]
Interferon gamma receptor 2 (IFNGR2) OTVOPCHW INGR2_HUMAN Increases Expression [8]
Cyclin-dependent kinase inhibitor 1 (CDKN1A) OTQWHCZE CDN1A_HUMAN Decreases Expression [8]
Collagen alpha-1(XVIII) chain (COL18A1) OTJFUH6O COIA1_HUMAN Decreases Expression [8]
Large ribosomal subunit protein eL28 (RPL28) OTEVRCBO RL28_HUMAN Increases Expression [8]
Microtubule-associated protein 1B (MAP1B) OTVXW089 MAP1B_HUMAN Increases Expression [8]
Phosphatidylinositol 5-phosphate 4-kinase type-2 alpha (PIP4K2A) OTO9JO9U PI42A_HUMAN Increases Expression [8]
Homeobox protein MOX-1 (MEOX1) OTJEMT2D MEOX1_HUMAN Decreases Expression [7]
Small ribosomal subunit protein mS29 (DAP3) OTNPEZYM RT29_HUMAN Increases Expression [8]
Integrin alpha-8 (ITGA8) OTBH8WFD ITA8_HUMAN Increases Expression [8]
Fibroblast growth factor 8 (FGF8) OTFU0IUW FGF8_HUMAN Increases Expression [7]
Neurotrypsin (PRSS12) OT1MYL3L NETR_HUMAN Increases Expression [8]
Protein S100-A10 (S100A10) OTI71243 S10AA_HUMAN Increases Expression [8]
Disintegrin and metalloproteinase domain-containing protein 8 (ADAM8) OT24S8YN ADAM8_HUMAN Decreases Expression [8]
Glutathione S-transferase omega-1 (GSTO1) OTUJ93MN GSTO1_HUMAN Decreases Expression [8]
Transcription factor Sp3 (SP3) OTYDQZ1T SP3_HUMAN Increases Expression [8]
Urokinase plasminogen activator surface receptor (PLAUR) OTIRKKEQ UPAR_HUMAN Decreases Expression [8]
Fibromodulin (FMOD) OT9EJ5H8 FMOD_HUMAN Decreases Expression [8]
Potassium voltage-gated channel subfamily H member 2 (KCNH2) OTZX881H KCNH2_HUMAN Decreases Activity [41]
Transcription factor 15 (TCF15) OTA6UCWC TCF15_HUMAN Decreases Expression [7]
Phosphatidate phosphatase LPIN1 (LPIN1) OTQ75KF2 LPIN1_HUMAN Increases Expression [8]
Signal transducer and activator of transcription 4 (STAT4) OTAK3VFR STAT4_HUMAN Decreases Expression [8]
Nuclear receptor subfamily 1 group I member 3 (NR1I3) OTS3SGH7 NR1I3_HUMAN Increases Activity [42]
Oligodendrocyte transcription factor 3 (OLIG3) OTU8XLAF OLIG3_HUMAN Increases Expression [7]
Caspase-10 (CASP10) OTE6J88E CASPA_HUMAN Increases Expression [8]
Sodium channel protein type 2 subunit alpha (SCN2A) OTUSYE4Z SCN2A_HUMAN Decreases Activity [43]
Eyes absent homolog 1 (EYA1) OTHU807A EYA1_HUMAN Decreases Expression [7]
Forkhead box protein C2 (FOXC2) OT83P1E0 FOXC2_HUMAN Decreases Expression [7]
Angiotensin-converting enzyme 2 (ACE2) OTTRZGU7 ACE2_HUMAN Decreases Expression [44]
Neurogenin-2 (NEUROG2) OTAEMIGT NGN2_HUMAN Increases Expression [7]
Sodium channel protein type 3 subunit alpha (SCN3A) OT4C2LCB SCN3A_HUMAN Affects Binding [45]
Death-associated protein kinase 2 (DAPK2) OTWODUQG DAPK2_HUMAN Decreases Expression [8]
Structural maintenance of chromosomes protein 3 (SMC3) OTWGFRHD SMC3_HUMAN Increases Expression [8]
Glutathione S-transferase kappa 1 (GSTK1) OTDNGWAF GSTK1_HUMAN Decreases Expression [8]
Adiponectin receptor protein 2 (ADIPOR2) OT2HDTL8 PAQR2_HUMAN Increases ADR [9]
Epoxide hydrolase 1 (EPHX1) OTBKWQER HYEP_HUMAN Affects Response To Substance [46]
Protein kinase C-binding protein NELL1 (NELL1) OTF3TX3N NELL1_HUMAN Increases ADR [9]
Alkaline phosphatase, tissue-nonspecific isozyme (ALPL) OTG7J4BP PPBT_HUMAN Increases ADR [47]
Sodium channel subunit beta-1 (SCN1B) OTGD78J3 SCN1B_HUMAN Decreases Response To Substance [45]
Bis(5'-adenosyl)-triphosphatase (FHIT) OTGWBSLA FHIT_HUMAN Increases ADR [9]
Catalase (CAT) OTHEBX9R CATA_HUMAN Decreases Response To Substance [48]
Sodium channel protein type 1 subunit alpha (SCN1A) OTJ9ZTYI SCN1A_HUMAN Affects Response To Substance [49]
Dachshund homolog 1 (DACH1) OTMKNAGG DACH1_HUMAN Increases ADR [9]
V-type proton ATPase subunit d 2 (ATP6V0D2) OTMOZJO0 VA0D2_HUMAN Increases ADR [9]
Alanine aminotransferase 1 (GPT) OTOXOA0Q ALAT1_HUMAN Increases ADR [47]
Bifunctional epoxide hydrolase 2 (EPHX2) OTPTRCNW HYES_HUMAN Increases ADR [47]
Atrial natriuretic peptide receptor 1 (NPR1) OTRWART5 ANPRA_HUMAN Increases ADR [47]
A disintegrin and metalloproteinase with thrombospondin motifs 20 (ADAMTS20) OTU0EKLN ATS20_HUMAN Increases ADR [9]
Probable E3 ubiquitin-protein ligase IRF2BPL (IRF2BPL) OTV8MNT1 I2BPL_HUMAN Increases ADR [9]
Glutathione hydrolase 7 (GGT7) OTW4IO3I GGT7_HUMAN Increases ADR [47]
cAMP-dependent protein kinase type II-beta regulatory subunit (PRKAR2B) OTZEXEFH KAP3_HUMAN Increases ADR [9]
Cytochrome P450 2D6 (CYP2D6) OTZJC802 CP2D6_HUMAN Increases ADR [47]
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⏷ Show the Full List of 122 DOT(s)
Indication(s) of Valproic Acid
Disease Entry ICD 11 Status REF
Absence epilepsy N.A. Approved [4]
Epilepsy 8A60-8A68 Approved [4]
Glioblastoma 2A00 Approved [4]
Coronavirus Disease 2019 (COVID-19) 1D6Y Investigative [5]
Neuroblastoma 2D11.2 Investigative [4]

References

1 ClinicalTrials.gov (NCT05697614) The Benefit and Safety of Older Generation Anti-Epileptic Drugs (AEDs) in Drug-Resistant Epilepsy Children
2 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
3 Phenytoin FDA Label
4 Valproic Acid FDA Label
5 Immunopharmacological management of COVID-19: Potential therapeutic role of valproic acid. Med Hypotheses. 2020 May 27;143:109891.
6 Expression and inducibility of the human bilirubin UDP-glucuronosyltransferase UGT1A1 in liver and cultured primary hepatocytes: evidence for both genetic and environmental influences. Hepatology. 1999 Aug;30(2):476-84.
7 Exposure-based assessment of chemical teratogenicity using morphogenetic aggregates of human embryonic stem cells. Reprod Toxicol. 2020 Jan;91:74-91. doi: 10.1016/j.reprotox.2019.10.004. Epub 2019 Nov 8.
8 Role of phenytoin in wound healing: microarray analysis of early transcriptional responses in human dermal fibroblasts. Biochem Biophys Res Commun. 2004 Feb 13;314(3):661-6. doi: 10.1016/j.bbrc.2003.12.146.
9 Genome-wide mapping for clinically relevant predictors of lamotrigine- and phenytoin-induced hypersensitivity reactions. Pharmacogenomics. 2012 Mar;13(4):399-405. doi: 10.2217/pgs.11.165.
10 Lacosamide: a new approach to target voltage-gated sodium currents in epileptic disorders. CNS Drugs. 2009;23(7):555-68.
11 Evaluation of transport of common antiepileptic drugs by human multidrug resistance-associated proteins (MRP1, 2 and 5) that are overexpressed in pharmacoresistant epilepsy. Neuropharmacology. 2010 Jun;58(7):1019-32.
12 Upregulation of brain expression of P-glycoprotein in MRP2-deficient TR(-) rats resembles seizure-induced up-regulation of this drug efflux transporter in normal rats. Epilepsia. 2007 Apr;48(4):631-45.
13 The transport of antiepileptic drugs by P-glycoprotein. Adv Drug Deliv Rev. 2012 Jul;64(10):930-42.
14 Coadministration of lopinavir/ritonavir and phenytoin results in two-way drug interaction through cytochrome P-450 induction. J Acquir Immune Defic Syndr. 2004 Aug 15;36(5):1034-40.
15 Comparison of basal glutathione S-transferase activities and of the influence of phenobarbital, butylated hydroxy-anisole or 5,5'-diphenylhydantoin on enzyme activity in male rodents. Comp Biochem Physiol C. 1987;88(1):91-3.
16 PharmGKB summary: phenytoin pathway. Pharmacogenet Genomics. 2012 Jun;22(6):466-70.
17 Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
18 Antiepileptic drug interactions - principles and clinical implications. Curr Neuropharmacol. 2010 Sep;8(3):254-67.
19 A reporter gene assay to assess the molecular mechanisms of xenobiotic-dependent induction of the human CYP3A4 gene in vitro. Xenobiotica. 1999 Mar;29(3):269-79.
20 Effects of phenytoin on glutathione status and oxidative stress biomarker gene mRNA levels in cultured precision human liver slices. Toxicol Sci. 2001 Jan;59(1):118-26.
21 Induction of CYP3As in HepG2 cells by several drugs. Association between induction of CYP3A4 and expression of glucocorticoid receptor. Biol Pharm Bull. 2003 Apr;26(4):510-7.
22 Human constitutive androstane receptor mediates induction of CYP2B6 gene expression by phenytoin. J Biol Chem. 2004 Jul 9;279(28):29295-301. doi: 10.1074/jbc.M400580200. Epub 2004 Apr 28.
23 The effects of genetic polymorphisms of CYP2C9 and CYP2C19 on phenytoin metabolism in Japanese adult patients with epilepsy: studies in stereoselective hydroxylation and population pharmacokinetics. Epilepsia. 1998 Dec;39(12):1317-23. doi: 10.1111/j.1528-1157.1998.tb01330.x.
24 CYP2C9, CYP2C19, ABCB1 (MDR1) genetic polymorphisms and phenytoin metabolism in a Black Beninese population. Pharmacogenet Genomics. 2005 Nov;15(11):779-86.
25 Intestinal expression of cytochrome P450 enzymes and ABC transporters and carbamazepine and phenytoin disposition. Acta Neurol Scand. 2007 Apr;115(4):232-42. doi: 10.1111/j.1600-0404.2006.00761.x.
26 Common risk allele in aromatic antiepileptic-drug induced Stevens-Johnson syndrome and toxic epidermal necrolysis in Han Chinese. Pharmacogenomics. 2010 Mar;11(3):349-56. doi: 10.2217/pgs.09.162.
27 Prediction of aryl hydrocarbon receptor-mediated enzyme induction of drugs and chemicals by mRNA quantification. Chem Res Toxicol. 1998 Dec;11(12):1447-52.
28 CYP3A4 induction by drugs: correlation between a pregnane X receptor reporter gene assay and CYP3A4 expression in human hepatocytes. Drug Metab Dispos. 2002 Jul;30(7):795-804.
29 Inhibition of human aromatase complex (CYP19) by antiepileptic drugs. Toxicol In Vitro. 2008 Feb;22(1):146-53.
30 Roles of nitric oxide in inflammatory downregulation of human cytochromes P450. Free Radic Biol Med. 2008 Mar 15;44(6):1161-8.
31 Antiepileptic drugs: impacts on human serum paraoxonase-1. J Biochem Mol Toxicol. 2017 Jun;31(6).
32 Phenytoin and cyclosporin A suppress the expression of MMP-1, TIMP-1, and cathepsin L, but not cathepsin B in cultured gingival fibroblasts. J Periodontol. 2000 Jun;71(6):955-60. doi: 10.1902/jop.2000.71.6.955.
33 Immunolocalizaiton of c-Myc and bcl-2 proto-oncogene products in gingival hyperplasia induced by nifedipine and phenytoin. J Periodontol. 2000 Jan;71(1):44-9. doi: 10.1902/jop.2000.71.1.44.
34 Phenytoin induced vitamin D deficiency presenting as proximal muscle weakness. Indian Pediatr. 2010 Jul;47(7):624-5. doi: 10.1007/s13312-010-0121-3.
35 Interleukin-1 beta and phenytoin reduce alpha 1 (I) procollagen mRNA expression in human gingival fibroblasts. J Periodontal Res. 1996 Nov;31(8):563-9. doi: 10.1111/j.1600-0765.1996.tb00521.x.
36 Impaired degradation of matrix collagen in human gingival fibroblasts by the antiepileptic drug phenytoin. J Periodontol. 2005 Jun;76(6):941-50. doi: 10.1902/jop.2005.76.6.941.
37 Myopathy and hypersensitivity to phenytoin. Neurology. 1983 Jun;33(6):790-1. doi: 10.1212/wnl.33.6.790.
38 Increased expression of type VI collagen genes in drug-induced gingival enlargement. FEBS Lett. 1993 Nov 8;334(1):65-8. doi: 10.1016/0014-5793(93)81681-o.
39 Phenytoin may increase the efficacy of temozolomide by methylating DNA-repair enzyme, O6-methylguanine-DNA methyltransferase in patients with glioblastoma. Med Hypotheses. 2005;65(4):819-20. doi: 10.1016/j.mehy.2005.04.007.
40 Up-regulation of keratinocyte growth factor and receptor: a possible mechanism of action of phenytoin in wound healing. Biochem Biophys Res Commun. 2001 Apr 13;282(4):875-81. doi: 10.1006/bbrc.2001.4621.
41 Identification of human Ether--go-go related gene modulators by three screening platforms in an academic drug-discovery setting. Assay Drug Dev Technol. 2010 Dec;8(6):727-42. doi: 10.1089/adt.2010.0331.
42 Modulation of UDP-glucuronosyltransferase 1A1 in primary human hepatocytes by prototypical inducers. J Biochem Mol Toxicol. 2005;19(2):96-108. doi: 10.1002/jbt.20058.
43 Electrophysiological and pharmacological properties of the human brain type IIA Na+ channel expressed in a stable mammalian cell line. Pflugers Arch. 2001 Jan;441(4):425-33. doi: 10.1007/s004240000448.
44 Effect of common medications on the expression of SARS-CoV-2 entry receptors in liver tissue. Arch Toxicol. 2020 Dec;94(12):4037-4041. doi: 10.1007/s00204-020-02869-1. Epub 2020 Aug 17.
45 An epilepsy mutation in the beta1 subunit of the voltage-gated sodium channel results in reduced channel sensitivity to phenytoin. Epilepsy Res. 2005 May;64(3):77-84. doi: 10.1016/j.eplepsyres.2005.03.003.
46 Maternal EPHX1 polymorphisms and risk of phenytoin-induced congenital malformations. Pharmacogenet Genomics. 2010 Jan;20(1):58-63. doi: 10.1097/FPC.0b013e328334b6a3.
47 ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.
48 Embryoprotective role of endogenous catalase in acatalasemic and human catalase-expressing mouse embryos exposed in culture to developmental and phenytoin-enhanced oxidative stress. Toxicol Sci. 2011 Apr;120(2):428-38. doi: 10.1093/toxsci/kfr007. Epub 2011 Jan 20.
49 A common polymorphism in the SCN1A gene associates with phenytoin serum levels at maintenance dose. Pharmacogenet Genomics. 2006 Oct;16(10):721-6. doi: 10.1097/01.fpc.0000230114.41828.73.