Details of the Drug

General Information of Drug (ID: DMXOELT)

Drug Name
Midazolam
Synonyms
Dazolam; Dormicum; Midanium; Midazolamum; Midosed; Versed; Midazolam Base; Dormicum (TN); Hypnovel (TN); Midacum (TN); Midazolamum [INN-Latin]; Ro 21-3981; Versed (TN); Midazolam (JAN/INN); Midazolam [INN:BAN:JAN]; 4H-Imidazo[1,5-a][1,4]benzodiazepine, 8-chloro-6-(2-fluoro-phenyl)-1-methyl-, (Z)-2-butenedioate; 8-Chlor-6-(2-fluorphenyl)-1-methyl-4H-imidazo(1,5-a)(1,4)benzodiazepin; 8-Chloro-6-(2-fluorophenyl)-1-methyl-4H-imidazo[1,5-a][1,4]benzodiazepine; 8-Chloro-6-(2-fluorophenyl)-1-methyl-4H-imidazo[1,5a][1,4]benzodiazepine hydrochloride; 8-Chloro-6-(O-fluorophenyl)-1-methyl-4H-imidazo[1,5-a][1,4]-benzodiazepine; 8-Chloro-6-(o-fluorophenyl)-1-methyl-4H-imidazo(1,5-a)(1,4)benzodiazepine
Indication
Disease Entry ICD 11 Status REF
Irritability MB24 Approved [1], [2]
Epilepsy 8A60-8A68 Phase 3 [3]
Therapeutic Class
Hypnotics and Sedatives
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 325.8
Topological Polar Surface Area (xlogp) 2.5
Rotatable Bond Count (rotbonds) 1
Hydrogen Bond Donor Count (hbonddonor) 0
Hydrogen Bond Acceptor Count (hbondacc) 3
ADMET Property
Absorption Cmax
The maximum plasma concentration (Cmax) of drug is 90 mcg/L [4]
Absorption Tmax
The time to maximum plasma concentration (Tmax) is 0.5 h [4]
BDDCS Class
Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 1: high solubility and high permeability [5]
Bioavailability
The bioavailability of drug is 90% [4]
Clearance
The total body clearance of drug is 367.3 mL/h/kg [6]
Elimination
0.5% of drug is excreted via urine [6]
Half-life
The concentration or amount of drug in body reduced by one-half in 1.8 - 6.4 hours [7]
Metabolism
The drug is metabolized via the liver [4]
MRTD
The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 0.2557 micromolar/kg/day [8]
Unbound Fraction
The unbound fraction of drug in plasma is 0.017% [9]
Vd
The volume of distribution (Vd) of drug is 2.117 L/kg [6]
Water Solubility
The ability of drug to dissolve in water is measured as 10.3 mg/mL [5]
Chemical Identifiers
Formula
C18H13ClFN3
IUPAC Name
8-chloro-6-(2-fluorophenyl)-1-methyl-4H-imidazo[1,5-a][1,4]benzodiazepine
Canonical SMILES
CC1=NC=C2N1C3=C(C=C(C=C3)Cl)C(=NC2)C4=CC=CC=C4F
InChI
InChI=1S/C18H13ClFN3/c1-11-21-9-13-10-22-18(14-4-2-3-5-16(14)20)15-8-12(19)6-7-17(15)23(11)13/h2-9H,10H2,1H3
InChIKey
DDLIGBOFAVUZHB-UHFFFAOYSA-N
Cross-matching ID
PubChem CID
4192
ChEBI ID
CHEBI:6931
CAS Number
59467-70-8
DrugBank ID
DB00683
TTD ID
D0U6LM
VARIDT ID
DR00684
INTEDE ID
DR1086

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Translocator protein (TSPO) TTPTXIN TSPO_HUMAN Modulator [10]

Drug Transporter (DTP)
DTP Name DTP ID UniProt ID MOA REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [11]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Cytochrome P450 3A4 (CYP3A4)
Main DME 		DE4LYSA CP3A4_HUMAN Substrate [12]
Cytochrome P450 3A5 (CYP3A5) DEIBDNY CP3A5_HUMAN Substrate [13]
Cytochrome P450 2B6 (CYP2B6) DEPKLMQ CP2B6_HUMAN Substrate [14]
Cytochrome P450 3A7 (CYP3A7) DERD86B CP3A7_HUMAN Substrate [15]
Cytochrome P450 4B1 (CYP4B1) DEMF740 CP4B1_HUMAN Substrate [15]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Irritability
ICD Disease Classification MB24
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
Translocator protein (TSPO) DTT TSPO 3.93E-10 0.43 1.02
P-glycoprotein 1 (ABCB1) DTP P-GP 9.39E-02 1.07E-01 2.80E-01
Cytochrome P450 2B6 (CYP2B6) DME CYP2B6 4.88E-01 -1.69E-05 -1.28E-04
Cytochrome P450 4B1 (CYP4B1) DME CYP4B1 3.90E-02 5.64E-02 3.35E-01
Cytochrome P450 3A5 (CYP3A5) DME CYP3A5 9.96E-01 -3.17E-03 -1.84E-02
Cytochrome P450 3A4 (CYP3A4) DME CYP3A4 1.04E-02 6.29E-02 3.54E-01
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Midazolam (Comorbidity)
DDI Drug Name DDI Drug ID Severity Mechanism Comorbidity REF
Sodium bicarbonate DMMU6BJ Minor Altered absorption of Midazolam due to GI dynamics variation caused by Sodium bicarbonate. Acidosis [5C73] [60]
Ivosidenib DM8S6T7 Moderate Increased metabolism of Midazolam caused by Ivosidenib mediated induction of CYP450 enzyme. Acute myeloid leukaemia [2A60] [61]
Emapalumab DMZG5WL Moderate Altered metabolism of Midazolam due to Emapalumab alters the formation of CYP450 enzymes. Adaptive immunity immunodeficiency [4A01] [62]
Siltuximab DMGEATB Moderate Altered metabolism of Midazolam due to Siltuximab alters the formation of CYP450 enzymes. Anemia [3A00-3A9Z] [62]
Dronedarone DMA8FS5 Moderate Decreased metabolism of Midazolam caused by Dronedarone mediated inhibition of CYP450 enzyme. Angina pectoris [BA40] [63]
Posaconazole DMUL5EW Major Decreased metabolism of Midazolam caused by Posaconazole mediated inhibition of CYP450 enzyme. Aspergillosis [1F20] [64]
Dalfopristin DM4LTKV Moderate Decreased metabolism of Midazolam caused by Dalfopristin mediated inhibition of CYP450 enzyme. Bacterial infection [1A00-1C4Z] [65]
Clarithromycin DM4M1SG Moderate Decreased metabolism of Midazolam caused by Clarithromycin mediated inhibition of CYP450 enzyme. Bacterial infection [1A00-1C4Z] [64]
Troleandomycin DMUZNIG Moderate Decreased metabolism of Midazolam caused by Troleandomycin mediated inhibition of CYP450 enzyme. Bacterial infection [1A00-1C4Z] [66]
Telithromycin DMZ4P3A Major Decreased metabolism of Midazolam caused by Telithromycin mediated inhibition of CYP450 enzyme. Bacterial infection [1A00-1C4Z] [67]
Erdafitinib DMI782S Moderate Increased metabolism of Midazolam caused by Erdafitinib mediated induction of CYP450 enzyme. Bladder cancer [2C94] [68]
Lapatinib DM3BH1Y Moderate Decreased metabolism of Midazolam caused by Lapatinib mediated inhibition of CYP450 enzyme. Breast cancer [2C60-2C6Y] [69]
Tucatinib DMBESUA Major Decreased metabolism of Midazolam caused by Tucatinib mediated inhibition of CYP450 enzyme. Breast cancer [2C60-2C6Y] [70]
Palbociclib DMD7L94 Moderate Decreased metabolism of Midazolam caused by Palbociclib mediated inhibition of CYP450 enzyme. Breast cancer [2C60-2C6Y] [71]
Atorvastatin DMF28YC Moderate Decreased metabolism of Midazolam caused by Atorvastatin mediated inhibition of CYP450 enzyme. Cardiovascular disease [BA00-BE2Z] [72]
Olopatadine DMKMWQG Moderate Additive CNS depression effects by the combination of Midazolam and Olopatadine. Conjunctiva disorder [9A60] [73]
Propofol DMB4OLE Moderate Additive cardiorespiratory depression effects by the combination of Midazolam and Propofol. Corneal disease [9A76-9A78] [74]
Alfentanil DMVO0UB Moderate Decreased metabolism of Midazolam caused by Alfentanil mediated inhibition of CYP450 enzyme. Corneal disease [9A76-9A78] [75]
Mifepristone DMGZQEF Major Decreased metabolism of Midazolam caused by Mifepristone mediated inhibition of CYP450 enzyme. Cushing syndrome [5A70] [76]
Lumacaftor DMCLWDJ Major Increased metabolism of Midazolam caused by Lumacaftor mediated induction of CYP450 enzyme. Cystic fibrosis [CA25] [64]
Ivacaftor DMZC1HS Moderate Decreased clearance of Midazolam due to the transporter inhibition by Ivacaftor. Cystic fibrosis [CA25] [77]
Ethanol DMDRQZU Moderate Additive CNS depression effects by the combination of Midazolam and Ethanol. Cystitis [GC00] [78]
MK-8228 DMOB58Q Moderate Decreased metabolism of Midazolam caused by MK-8228 mediated inhibition of CYP450 enzyme. Cytomegaloviral disease [1D82] [79]
Nefazodone DM4ZS8M Moderate Decreased metabolism of Midazolam caused by Nefazodone mediated inhibition of CYP450 enzyme. Depression [6A70-6A7Z] [80]
Esketamine DMVU687 Moderate Additive CNS depression effects by the combination of Midazolam and Esketamine. Depression [6A70-6A7Z] [64]
SODIUM CITRATE DMHPD2Y Minor Altered absorption of Midazolam due to GI dynamics variation caused by SODIUM CITRATE. Discovery agent [N.A.] [60]
Oxcarbazepine DM5PU6O Moderate Increased metabolism of Midazolam caused by Oxcarbazepine mediated induction of CYP450 enzyme. Epilepsy/seizure [8A61-8A6Z] [81]
Cenobamate DMGOVHA Moderate Increased metabolism of Midazolam caused by Cenobamate mediated induction of CYP450 enzyme. Epilepsy/seizure [8A61-8A6Z] [82]
Stiripentol DMMSDOY Moderate Decreased metabolism of Midazolam caused by Stiripentol mediated inhibition of CYP450 enzyme. Epilepsy/seizure [8A61-8A6Z] [83]
Fosphenytoin DMOX3LB Moderate Increased metabolism of Midazolam caused by Fosphenytoin mediated induction of CYP450 enzyme. Epilepsy/seizure [8A61-8A6Z] [84]
Rufinamide DMWE60C Moderate Increased metabolism of Midazolam caused by Rufinamide mediated induction of CYP450 enzyme. Epilepsy/seizure [8A61-8A6Z] [62]
Tazemetostat DMWP1BH Moderate Increased metabolism of Midazolam caused by Tazemetostat mediated induction of CYP450 enzyme. Follicular lymphoma [2A80] [85]
Itraconazole DMCR1MV Major Decreased metabolism of Midazolam caused by Itraconazole mediated inhibition of CYP450 enzyme. Fungal infection [1F29-1F2F] [70]
Ketoconazole DMPZI3Q Major Decreased metabolism of Midazolam caused by Ketoconazole mediated inhibition of CYP450 enzyme. Fungal infection [1F29-1F2F] [70]
Boceprevir DMBSHMF Major Decreased metabolism of Midazolam caused by Boceprevir mediated inhibition of CYP450 enzyme. Hepatitis virus infection [1E50-1E51] [86]
Simeprevir DMLUA9D Moderate Decreased metabolism of Midazolam caused by Simeprevir mediated inhibition of CYP450 enzyme. Hepatitis virus infection [1E50-1E51] [87]
Telaprevir DMMRV29 Major Decreased metabolism of Midazolam caused by Telaprevir mediated inhibition of CYP450 enzyme. Hepatitis virus infection [1E50-1E51] [86]
Rifampin DMA8J1G Minor Increased metabolism of Midazolam caused by Rifampin mediated induction of CYP450 enzyme. HIV-infected patients with tuberculosis [1B10-1B14] [88]
Rifapentine DMCHV4I Moderate Increased metabolism of Midazolam caused by Rifapentine mediated induction of CYP450 enzyme. HIV-infected patients with tuberculosis [1B10-1B14] [89]
Delavirdine DM3NF5G Major Decreased metabolism of Midazolam caused by Delavirdine mediated inhibition of CYP450 enzyme. Human immunodeficiency virus disease [1C60-1C62] [90]
Fosamprenavir DM4W9B3 Major Decreased metabolism of Midazolam caused by Fosamprenavir mediated inhibition of CYP450 enzyme. Human immunodeficiency virus disease [1C60-1C62] [91]
Saquinavir DMG814N Major Decreased metabolism of Midazolam caused by Saquinavir mediated inhibition of CYP450 enzyme. Human immunodeficiency virus disease [1C60-1C62] [91]
Didanosine DMI2QPE Minor Altered absorption of Midazolam due to GI dynamics variation caused by Didanosine. Human immunodeficiency virus disease [1C60-1C62] [60]
Amprenavir DMLMXE0 Major Decreased metabolism of Midazolam caused by Amprenavir mediated inhibition of CYP450 enzyme. Human immunodeficiency virus disease [1C60-1C62] [91]
Darunavir DMN3GCH Major Decreased metabolism of Midazolam caused by Darunavir mediated inhibition of CYP450 enzyme. Human immunodeficiency virus disease [1C60-1C62] [91]
Atazanavir DMSYRBX Major Decreased metabolism of Midazolam caused by Atazanavir mediated inhibition of CYP450 enzyme. Human immunodeficiency virus disease [1C60-1C62] [91]
Conivaptan DM1V329 Major Decreased metabolism of Midazolam caused by Conivaptan mediated inhibition of CYP450 enzyme. Hypo-osmolality/hyponatraemia [5C72] [92]
Probenecid DMMFWOJ Minor Decreased metabolism of Midazolam caused by Probenecid. Inborn purine/pyrimidine/nucleotide metabolism error [5C55] [93]
Lesinurad DMUR64T Moderate Increased metabolism of Midazolam caused by Lesinurad mediated induction of CYP450 enzyme. Inborn purine/pyrimidine/nucleotide metabolism error [5C55] [94]
Berotralstat DMWA2DZ Moderate Decreased metabolism of Midazolam caused by Berotralstat mediated inhibition of CYP450 enzyme. Innate/adaptive immunodeficiency [4A00] [95]
Glycerol phenylbutyrate DMDGRQO Moderate Increased metabolism of Midazolam caused by Glycerol phenylbutyrate mediated induction of CYP450 enzyme. Liver disease [DB90-DB9Z] [62]
Crizotinib DM4F29C Moderate Decreased metabolism of Midazolam caused by Crizotinib mediated inhibition of CYP450 enzyme. Lung cancer [2C25] [96]
Brigatinib DM7W94S Moderate Increased metabolism of Midazolam caused by Brigatinib mediated induction of CYP450 enzyme. Lung cancer [2C25] [97]
Ceritinib DMB920Z Major Decreased metabolism of Midazolam caused by Ceritinib mediated inhibition of CYP450 enzyme. Lung cancer [2C25] [70]
PF-06463922 DMKM7EW Moderate Increased metabolism of Midazolam caused by PF-06463922 mediated induction of CYP450 enzyme. Lung cancer [2C25] [98]
Osimertinib DMRJLAT Moderate Increased metabolism of Midazolam caused by Osimertinib mediated induction of CYP450 enzyme. Lung cancer [2C25] [62]
Selpercatinib DMZR15V Moderate Decreased metabolism of Midazolam caused by Selpercatinib mediated inhibition of CYP450 enzyme. Lung cancer [2C25] [62]
Idelalisib DM602WT Major Decreased metabolism of Midazolam caused by Idelalisib mediated inhibition of CYP450 enzyme. Mature B-cell leukaemia [2A82] [70]
IPI-145 DMWA24P Moderate Decreased metabolism of Midazolam caused by IPI-145 mediated inhibition of CYP450 enzyme. Mature B-cell leukaemia [2A82] [99]
Vemurafenib DM62UG5 Minor Increased metabolism of Midazolam caused by Vemurafenib mediated induction of CYP450 enzyme. Melanoma [2C30] [64]
LGX818 DMNQXV8 Moderate Increased metabolism of Midazolam caused by LGX818 mediated induction of CYP450 enzyme. Melanoma [2C30] [100]
Dabrafenib DMX6OE3 Moderate Increased metabolism of Midazolam caused by Dabrafenib mediated induction of CYP450 enzyme. Melanoma [2C30] [62]
Allopregnanolone DMNLHAC Moderate Additive CNS depression effects by the combination of Midazolam and Allopregnanolone. Mental/behavioural/neurodevelopmental disorder [6E20-6E8Z] [101]
Lasmiditan DMXLVDT Moderate Additive CNS depression effects by the combination of Midazolam and Lasmiditan. Migraine [8A80] [102]
Exjade DMHPRWG Moderate Decreased metabolism of Midazolam caused by Exjade mediated inhibition of CYP450 enzyme. Mineral absorption/transport disorder [5C64] [103]
Flibanserin DM70DTN Moderate Additive CNS depression effects by the combination of Midazolam and Flibanserin. Mood disorder [6A60-6E23] [104]
Thalidomide DM70BU5 Moderate Additive CNS depression effects by the combination of Midazolam and Thalidomide. Multiple myeloma [2A83] [105]
Fedratinib DM4ZBK6 Moderate Decreased metabolism of Midazolam caused by Fedratinib mediated inhibition of CYP450 enzyme. Myeloproliferative neoplasm [2A20] [62]
Dasatinib DMJV2EK Moderate Decreased metabolism of Midazolam caused by Dasatinib mediated inhibition of CYP450 enzyme. Myeloproliferative neoplasm [2A20] [106]
Modafinil DMYILBE Moderate Increased metabolism of Midazolam caused by Modafinil mediated induction of CYP450 enzyme. Narcolepsy [7A20] [64]
Teduglutide DMYOAKS Moderate Altered absorption of Midazolam caused by Teduglutide. Neonatal malabsorption syndrome [KB89] [107]
Levomethadyl Acetate DM06HG5 Major Additive CNS depression effects by the combination of Midazolam and Levomethadyl Acetate. Opioid use disorder [6C43] [104]
Apraclonidine DMO4PVE Moderate Additive CNS depression effects by the combination of Midazolam and Apraclonidine. Optic nerve disorder [9C40] [108]
Olaparib DM8QB1D Moderate Decreased metabolism of Midazolam caused by Olaparib mediated inhibition of CYP450 enzyme. Ovarian cancer [2C73] [64]
Rucaparib DM9PVX8 Moderate Decreased metabolism of Midazolam caused by Rucaparib mediated inhibition of CYP450 enzyme. Ovarian cancer [2C73] [109]
Abametapir DM2RX0I Moderate Decreased metabolism of Midazolam caused by Abametapir mediated inhibition of CYP450 enzyme. Pediculosis [1G00] [110]
Ranitidine DM0GUSX Moderate Increased metabolism of Midazolam caused by Ranitidine mediated induction of CYP450 enzyme. Peptic ulcer [DA61] [111]
Lonafarnib DMGM2Z6 Major Decreased metabolism of Midazolam caused by Lonafarnib mediated inhibition of CYP450 enzyme. Premature ageing appearance [LD2B] [112]
Enzalutamide DMGL19D Moderate Increased metabolism of Midazolam caused by Enzalutamide mediated induction of CYP450 enzyme. Prostate cancer [2C82] [64]
Ustekinumab DMHTYK3 Moderate Altered metabolism of Midazolam due to Ustekinumab alters the formation of CYP450 enzymes. Psoriasis [EA90] [62]
Ixekizumab DMXW92T Moderate Altered metabolism of Midazolam due to Ixekizumab alters the formation of CYP450 enzymes. Psoriasis [EA90] [62]
Temsirolimus DMS104F Moderate Increased plasma concentrations of Midazolam and Temsirolimus due to competitive inhibition of the same metabolic pathway. Renal cell carcinoma [2C90] [113]
Tocilizumab DM7J6OR Moderate Altered metabolism of Midazolam due to Tocilizumab alters the formation of CYP450 enzymes. Rheumatoid arthritis [FA20] [62]
Canakinumab DM8HLO5 Moderate Altered metabolism of Midazolam due to Canakinumab alters the formation of CYP450 enzymes. Rheumatoid arthritis [FA20] [62]
Rilonacept DMGLUQS Moderate Altered metabolism of Midazolam due to Rilonacept alters the formation of CYP450 enzymes. Rheumatoid arthritis [FA20] [62]
Golimumab DMHZV7X Moderate Altered metabolism of Midazolam due to Golimumab alters the formation of CYP450 enzymes. Rheumatoid arthritis [FA20] [62]
Sarilumab DMOGNXY Moderate Altered metabolism of Midazolam due to Sarilumab alters the formation of CYP450 enzymes. Rheumatoid arthritis [FA20] [62]
Voxelotor DMCS6M5 Moderate Decreased metabolism of Midazolam caused by Voxelotor mediated inhibition of CYP450 enzyme. Sickle-cell disorder [3A51] [114]
Telotristat ethyl DMDIYFZ Moderate Increased metabolism of Midazolam caused by Telotristat ethyl mediated induction of CYP450 enzyme. Small intestine developmental anomaly [DA90] [62]
Larotrectinib DM26CQR Moderate Decreased metabolism of Midazolam caused by Larotrectinib mediated inhibition of CYP450 enzyme. Solid tumour/cancer [2A00-2F9Z] [64]
Armodafinil DMGB035 Moderate Increased metabolism of Midazolam caused by Armodafinil mediated induction of CYP450 enzyme. Solid tumour/cancer [2A00-2F9Z] [64]
LEE011 DMMX75K Moderate Decreased metabolism of Midazolam caused by LEE011 mediated inhibition of CYP450 enzyme. Solid tumour/cancer [2A00-2F9Z] [115]
Pitolisant DM8RFNJ Moderate Increased metabolism of Midazolam caused by Pitolisant mediated induction of CYP450 enzyme. Somnolence [MG42] [62]
Fostamatinib DM6AUHV Moderate Decreased clearance of Midazolam due to the transporter inhibition by Fostamatinib. Thrombocytopenia [3B64] [116]
Brilinta DMBR01X Moderate Decreased metabolism of Midazolam caused by Brilinta mediated inhibition of CYP450 enzyme. Thrombosis [DB61-GB90] [62]
Tizanidine DMR2IQ4 Moderate Additive CNS depression effects by the combination of Midazolam and Tizanidine. Tonus and reflex abnormality [MB47] [117]
Sirolimus DMGW1ID Moderate Increased plasma concentrations of Midazolam and Sirolimus due to competitive inhibition of the same metabolic pathway. Transplant rejection [NE84] [113]
Tacrolimus DMZ7XNQ Moderate Increased plasma concentrations of Midazolam and Tacrolimus due to competitive inhibition of the same metabolic pathway. Transplant rejection [NE84] [113]
Amiodarone DMUTEX3 Minor Potentiate the pharmacologic effects by the combination of Midazolam and Amiodarone. Ventricular tachyarrhythmia [BC71] [118]
⏷ Show the Full List of 99 DDI Information of This Drug

References

1 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 3342).
2 FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (ANDA) 075154.
3 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
4 Cone EJ, Darwin WD, Gorodetzky CW, Tan T: Comparative metabolism of hydrocodone in man, rat, guinea pig, rabbit, and dog. Drug Metab Dispos. 1978 Jul-Aug;6(4):488-93.
5 BDDCS applied to over 900 drugs
6 An FDA phase I clinical trial of quinacrine sterilization (QS). Int J Gynaecol Obstet. 2003 Oct;83 Suppl 2:S45-9.
7 FDA approval: ado-trastuzumab emtansine for the treatment of patients with HER2-positive metastatic breast cancer. Clin Cancer Res. 2014 Sep 1;20(17):4436-41.
8 Estimating the safe starting dose in phase I clinical trials and no observed effect level based on QSAR modeling of the human maximum recommended daily dose
9 Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
10 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
11 A novel screening strategy to identify ABCB1 substrates and inhibitors. Naunyn Schmiedebergs Arch Pharmacol. 2009 Jan;379(1):11-26.
12 Selection of alternative CYP3A4 probe substrates for clinical drug interaction studies using in vitro data and in vivo simulation. Drug Metab Dispos. 2010 Jun;38(6):981-7.
13 In vitro metabolism of midazolam, triazolam, nifedipine, and testosterone by human liver microsomes and recombinant cytochromes p450: role of cyp3a4 and cyp3a5. Drug Metab Dispos. 2003 Jul;31(7):938-44.
14 Further characterization of the expression in liver and catalytic activity of CYP2B6. J Pharmacol Exp Ther. 1998 Sep;286(3):1253-9.
15 Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
16 Expression levels and activation of a PXR variant are directly related to drug resistance in osteosarcoma cell lines. Cancer. 2007 Mar 1;109(5):957-65.
17 Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47.
18 Comprehensive evaluation of tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: prominent roles for CYP3A and CYP2D6. J Pharmacol Exp Ther. 2004 Sep;310(3):1062-75.
19 Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
20 Metabolic interactions between acetaminophen (paracetamol) and two flavonoids, luteolin and quercetin, through in-vitro inhibition studies. J Pharm Pharmacol. 2017 Dec;69(12):1762-1772.
21 Potent mechanism-based inhibition of CYP3A4 by imatinib explains its liability to interact with CYP3A4 substrates. Br J Pharmacol. 2012 Apr;165(8):2787-98.
22 Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
23 The metabolism of zidovudine by human liver microsomes in vitro: formation of 3'-amino-3'-deoxythymidine. Biochem Pharmacol. 1994 Jul 19;48(2):267-76.
24 Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.
25 Steroid hormone hydroxylase specificities of eleven cDNA-expressed human cytochrome P450s. Arch Biochem Biophys. 1991 Oct;290(1):160-6.
26 Drug related genetic polymorphisms affecting adverse reactions to methotrexate, vinblastine, doxorubicin and cisplatin in patients with urothelial cancer. J Urol. 2008 Dec;180(6):2389-95.
27 Human prostate CYP3A5: identification of a unique 5'-untranslated sequence and characterization of purified recombinant protein. Biochem Biophys Res Commun. 1999 Jul 14;260(3):676-81.
28 Polymorphisms in cytochrome P4503A5 (CYP3A5) may be associated with race and tumor characteristics, but not metabolism and side effects of tamoxifen in breast cancer patients. Cancer Lett. 2005 Jan 10;217(1):61-72.
29 Drug Interactions Flockhart Table
30 Induction of hepatic CYP2E1 by a subtoxic dose of acetaminophen in rats: increase in dichloromethane metabolism and carboxyhemoglobin elevation. Drug Metab Dispos. 2007 Oct;35(10):1754-8.
31 Urinary 6 beta-hydroxycortisol excretion in rheumatoid arthritis. Br J Rheumatol. 1997 Jan;36(1):54-8.
32 Clinical pharmacokinetics of imatinib. Clin Pharmacokinet. 2005;44(9):879-94.
33 Kinetics and regulation of cytochrome P450-mediated etoposide metabolism. Drug Metab Dispos. 2004 Sep;32(9):993-1000.
34 Differential mechanism-based inhibition of CYP3A4 and CYP3A5 by verapamil. Drug Metab Dispos. 2005 May;33(5):664-71.
35 The role of cytochrome P450 3A (CYP3A) isoform(s) in oxidative metabolism of testosterone and benzphetamine in human adult and fetal liver. J Steroid Biochem Mol Biol. 1993 Jan;44(1):61-7.
36 Prediction of cytochrome P450 3A inhibition by verapamil enantiomers and their metabolites. Drug Metab Dispos. 2004 Feb;32(2):259-66.
37 The role of human cytochrome P450 enzymes in the formation of 2-hydroxymetronidazole: CYP2A6 is the high affinity (low Km) catalyst. Drug Metab Dispos. 2013 Sep;41(9):1686-94.
38 Effect of tamoxifen on the enzymatic activity of human cytochrome CYP2B6. J Pharmacol Exp Ther. 2002 Jun;301(3):945-52.
39 Hepatic metabolism of diclofenac: role of human CYP in the minor oxidative pathways. Biochem Pharmacol. 1999 Sep 1;58(5):787-96.
40 Characterization of the oxidative metabolites of 17beta-estradiol and estrone formed by 15 selectively expressed human cytochrome p450 isoforms. Endocrinology. 2003 Aug;144(8):3382-98.
41 Insights into CYP2B6-mediated drug-drug interactions. Acta Pharm Sin B. 2016 Sep;6(5):413-425.
42 Drugs that may have potential CYP2B6 interactions.
43 Involvement of human cytochrome P450 2B6 in the omega- and 4-hydroxylation of the anesthetic agent propofol. Xenobiotica. 2007 Jul;37(7):717-24.
44 Nicotine and 4-(methylnitrosamino)-1-(3-pyridyl)-butanone metabolism by cytochrome P450 2B6. Drug Metab Dispos. 2005 Dec;33(12):1760-4.
45 PharmGKB summary: phenytoin pathway. Pharmacogenet Genomics. 2012 Jun;22(6):466-70.
46 Application of the relative activity factor approach in scaling from heterologously expressed cytochromes p450 to human liver microsomes: studies on amitriptyline as a model substrate. J Pharmacol Exp Ther. 2001 Apr;297(1):326-37.
47 Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
48 MDR1 (ABCB1) G1199A (Ser400Asn) polymorphism alters transepithelial permeability and sensitivity to anticancer agents. Cancer Chemother Pharmacol. 2009 Jun;64(1):183-8.
49 Mammalian drug efflux transporters of the ATP binding cassette (ABC) family in multidrug resistance: A review of the past decade. Cancer Lett. 2016 Jan 1;370(1):153-64.
50 Folate transporter expression decreases in the human placenta throughout pregnancy and in pre-eclampsia. Pregnancy Hypertens. 2012 Apr;2(2):123-31.
51 Comparative studies on in vitro methods for evaluating in vivo function of MDR1 P-glycoprotein. Pharm Res. 2001 Dec;18(12):1660-8.
52 Antiestrogens and steroid hormones: substrates of the human P-glycoprotein. Biochem Pharmacol. 1994 Jul 19;48(2):287-92.
53 Association of genetic polymorphisms in the influx transporter SLCO1B3 and the efflux transporter ABCB1 with imatinib pharmacokinetics in patients with chronic myeloid leukemia. Ther Drug Monit. 2011 Apr;33(2):244-50.
54 Translocator protein (18 kDa) mediates the pro-growth effects of diazepam on Ehrlich tumor cells in vivo. Eur J Pharmacol. 2010 Jan 25;626(2-3):131-8.
55 Comparison of five benzodiazepine-receptor agonists on buprenorphine-induced mu-opioid receptor regulation. J Pharmacol Sci. 2009 May;110(1):36-46.
56 Effects of the combination of metyrapone and oxazepam on cocaine and food self-administration in rats. Pharmacol Biochem Behav. 2008 Nov;91(1):181-9.
57 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 2879).
58 Effects of benzodiazepines and non-benzodiazepine compounds on the GABA-induced response in frog isolated sensory neurones. Br J Pharmacol. 1989 Nov;98(3):735-40.
59 New hypnotics: perspectives from sleep physiology. Vertex. 2007 Jul-Aug;18(74):294-9.
60 Chun AH, Carrigan PJ, Hoffman DJ, Kershner RP, Stuart JD "Effect of antacids on absorption of clorazepate." Clin Pharmacol Ther 22 (1977): 329-35. [PMID: 19188]
61 Product Information. Tibsovo (ivosidenib). Agios Pharmaceuticals, Cambridge, MA.
62 Cerner Multum, Inc. "UK Summary of Product Characteristics.".
63 Product Information. Multaq (dronedarone). sanofi-aventis , Bridgewater, NJ.
64 Cerner Multum, Inc. "Australian Product Information.".
65 Product Information. Synercid (dalfopristin-quinupristin) Rhone-Poulenc Rorer, Collegeville, PA.
66 Amsden GW "Macrolides versus azalides: a drug interaction update." Ann Pharmacother 29 (1995): 906-17. [PMID: 8547740]
67 Product Information. Ketek (telithromycin). Aventis Pharmaceuticals, Bridgewater, NJ.
68 Product Information. Balversa (erdafitinib). Janssen Products, LP, Horsham, PA.
69 Product Information. Tykerb (lapatinib). Novartis Pharmaceuticals, East Hanover, NJ.
70 Ahonen J, Olkkola KT, Neuvonen PJ "Effect of itraconazole and terbinafine on the pharmacokinetics and pharmacodynamics of midazolam in healthy volunteers." Br J Clin Pharmacol 40 (1995): 270-2. [PMID: 8527290]
71 Product Information. Ibrance (palbociclib). Pfizer U.S. Pharmaceuticals Group, New York, NY.
72 Mc Donnell CG, Harte S, O'Driscoll J, O'Loughlin C, Van Pelt FD, Shorten GD "The effects of concurrent atorvastatin therapy on the pharmacokinetics of intravenous midazolam." Anaesthesia 58 (2003): 899-904. [PMID: 12911366]
73 Warrington SJ, Ankier SI, Turner P "Evaluation of possible interactions between ethanol and trazodone or amitriptyline." Neuropsychobiology 15 (1986): 31-7. [PMID: 3725002]
74 Gill SS, Wright EM, Reilly CS "Pharmacokinetic interaction of propofol and fentanyl: single bolus injection study." Br J Anaesth 65 (1990): 760-5. [PMID: 2265045]
75 Gilman AG, Rall TW, Nies AS, Taylor P, eds. "Goodman and Gilman's the Pharmacological Basis of Therapeutics. 8th ed." New York, NY: Pergamon Press Inc. (1990):.
76 He K, Woolf TF, Hollenberg PF "Mechanism-based inactivation of cytochrome P-450-3A4 by mifepristone (RU486)." J Pharmacol Exp Ther 288 (1999): 791-7. [PMID: 9918590]
77 Product Information. Kalydeco (ivacaftor). Vertex Pharmaceuticals, Cambridge, MA.
78 Divoll M, Greenblatt DJ, Lacasse Y, Shader RI "Benzodiazepine overdosage: plasma concentrations and clinical outcome." Psychopharmacology (Berl) 73 (1981): 381-3. [PMID: 6789361]
79 Product Information. Prevymis (letermovir). Merck & Company Inc, Whitehouse Station, NJ.
80 Barbhaiya RH, Shukla UA, Kroboth PD, Greene DS "Coadministration of nefazodone and benzodiazepines: 2. a pharmacokinetic interaction study with triazolam." J Clin Psychopharmacol 15 (1995): 320-6. [PMID: 8830062]
81 Product Information. Trileptal (oxcarbazepine) Novartis Pharmaceuticals, East Hanover, NJ.
82 Product Information. Xcopri (cenobamate). SK Life Science, Inc., Paramus, NJ.
83 EMEA. European Medicines Agency "EPARs. European Union Public Assessment Reports.".
84 Backman JT, Olkkola KT, Ojala M, Laaksovirta H, Neuvonen PJ "Concentrations and effects of oral midazolam are greatly reduced in patients treated with carbamazepine or phenytoin." Epilepsia 37 (1996): 253-7. [PMID: 8598183]
85 Product Information. Tazverik (tazemetostat). Epizyme, Inc, Cambridge, MA.
86 Product Information. Incivek (telaprevir). Vertex Pharmaceuticals, Cambridge, MA.
87 Product Information. Olysio (simeprevir). Janssen Pharmaceuticals, Titusville, NJ.
88 Ochs HR, Greenblatt DJ, Roberts GM, Dengler HJ "Diazepam interaction with antituberculosis drugs." Clin Pharmacol Ther 29 (1981): 671-8. [PMID: 7214796]
89 Product Information. Priftin (rifapentine). Hoechst Marion-Roussel Inc, Kansas City, MO.
90 Product Information. Rescriptor (delavirdine). Pharmacia and Upjohn, Kalamazoo, MI.
91 Barry M, Mulcahy F, Merry C, Gibbons S, Back D "Pharmacokinetics and potential interactions amongst antiretroviral agents used to treat patients with HIV infection." Clin Pharmacokinet 36 (1999): 289-304. [PMID: 10320951]
92 Product Information. Vaprisol (conivaptan). Cumberland Pharmaceuticals Inc, Nashville, TN.
93 Abernethy DR, Greenblatt DJ, Ameer B, Shader RI "Probenecid impairment of acetaminophen and lorazepam clearance: direct inhibition of ether glucuronide formation." J Pharmacol Exp Ther 234 (1985): 345-9. [PMID: 4020675]
94 Product Information. Zurampic (lesinurad). Astra-Zeneca Pharmaceuticals, Wilmington, DE.
95 Product Information. Orladeyo (berotralstat). BioCryst Pharmaceuticals Inc, Durham, NC.
96 Product Information. Xalkori (crizotinib). Pfizer U.S. Pharmaceuticals Group, New York, NY.
97 Product Information. Alunbrig (brigatinib). Ariad Pharmaceuticals Inc, Cambridge, MA.
98 Product Information. Lorbrena (lorlatinib). Pfizer U.S. Pharmaceuticals Group, New York, NY.
99 Product Information. Copiktra (duvelisib). Verastem, Inc., Needham, MA.
100 Product Information. Braftovi (encorafenib). Array BioPharma Inc., Boulder, CO.
101 Product Information. Zulresso (brexanolone). Sage Therapeutics, Inc., Cambridge, MA.
102 Product Information. Reyvow (lasmiditan). Lilly, Eli and Company, Indianapolis, IN.
103 Product Information. Exjade (deferasirox). Novartis Pharmaceuticals, East Hanover, NJ.
104 Product Information. Addyi (flibanserin). Sprout Pharmaceuticals, Raleigh, NC.
105 Product Information. Thalomid (thalidomide). Celgene Corporation, Warren, NJ.
106 Product Information. Sprycel (dasatinib). Bristol-Myers Squibb, Princeton, NJ.
107 Product Information. Gattex (teduglutide). NPS Pharmaceuticals, Bedminster, NJ.
108 Product Information. Alphagan (brimonidine ophthalmic). Allergan Inc, Irvine, CA.
109 EMA. European Medicines Agency. European Union "EMA - List of medicines under additional monitoring.".
110 Product Information. Xeglyze (abametapir topical). Dr. Reddy's Laboratories Inc, Upper Saddle River, NJ.
111 Product Information. Zantac (ranitidine). Glaxo Wellcome, Research Triangle Park, NC.
112 Backman JT, Kivisto KT, Olkkola KT, Neuvonen PJ "The area under the plasma concentration-time curve for oral midazolam is 400-fold larger during treatment with itraconazole than with rifampicin." Eur J Clin Pharmacol 54 (1998): 53-8. [PMID: 9591931]
113 Product Information. Prograf (tacrolimus). Fujisawa, Deerfield, IL.
114 Product Information. Oxbryta (voxelotor). Global Blood Therapeutics, Inc., South San Francisco, CA.
115 DSouza DL, Levasseur LM, Nezamis J, Robbins DK, Simms L, Koch KM "Effect of alosetron on the pharmacokinetics of alprazolam." J Clin Pharmacol 41 (2001): 452-4. [PMID: 11304902]
116 Product Information. Tavalisse (fostamatinib). Rigel Pharmaceuticals, South San Francisco, CA.
117 Product Information. Zanaflex (tizanidine). Acorda Therapeutics, Hawthorne, NY.
118 Kerin NZ, Aragon E, Faitel K, Frumin H, Rubenfire M "Long-term efficacy and toxicity of high- and low-dose amiodarone regimens." J Clin Pharmacol 29 (1989): 418-23. [PMID: 2661600]