General Information of Drug (ID: DM62UG5)

Drug Name
Vemurafenib
Synonyms PLX4032; RG7204; RO5185426; Zelboraf (TN); Vemurafenib (BRAF inhibitor)
Indication
Disease Entry ICD 11 Status REF
Melanoma 2C30 Approved [1], [2], [3]
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 489.9
Topological Polar Surface Area (xlogp) 5
Rotatable Bond Count (rotbonds) 7
Hydrogen Bond Donor Count (hbonddonor) 2
Hydrogen Bond Acceptor Count (hbondacc) 7
ADMET Property
Absorption AUC
The area under the plot of plasma concentration (AUC) of drug is 601 mgh/L [4]
Absorption Cmax
The maximum plasma concentration (Cmax) of drug is 62 mg/L [4]
BDDCS Class
Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 2: low solubility and high permeability [5]
Clearance
The total body clearance of drug is 31 L/day [6]
Elimination
Analysis showed that 94% of administered Vemurafenib is excreted via feces and 1% is excreted by urine [6]
Half-life
The concentration or amount of drug in body reduced by one-half in 57 hours [6]
Metabolism
The drug is metabolized via the CYP3A4 and the metabolites make up 5% of the components in plasma [6]
Vd
The volume of distribution (Vd) of drug is 106 L [6]
Chemical Identifiers
Formula
C23H18ClF2N3O3S
IUPAC Name
N-[3-[5-(4-chlorophenyl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]-2,4-difluorophenyl]propane-1-sulfonamide
Canonical SMILES
CCCS(=O)(=O)NC1=C(C(=C(C=C1)F)C(=O)C2=CNC3=C2C=C(C=N3)C4=CC=C(C=C4)Cl)F
InChI
InChI=1S/C23H18ClF2N3O3S/c1-2-9-33(31,32)29-19-8-7-18(25)20(21(19)26)22(30)17-12-28-23-16(17)10-14(11-27-23)13-3-5-15(24)6-4-13/h3-8,10-12,29H,2,9H2,1H3,(H,27,28)
InChIKey
GPXBXXGIAQBQNI-UHFFFAOYSA-N
Cross-matching ID
PubChem CID
42611257
ChEBI ID
CHEBI:63637
CAS Number
918504-65-1
DrugBank ID
DB08881
TTD ID
D0Y9EW
VARIDT ID
DR00711
INTEDE ID
DR1677
ACDINA ID
D00723

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Serine/threonine-protein kinase B-raf (BRAF) TTWCGQT BRAF_HUMAN Modulator [2]

Drug Transporter (DTP)
DTP Name DTP ID UniProt ID MOA REF
Organic anion transporting polypeptide 1B1 (SLCO1B1) DT3D8F0 SO1B1_HUMAN Substrate [7]
Organic anion transporting polypeptide 1B3 (SLCO1B3) DT9C1TS SO1B3_HUMAN Substrate [7]
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [8]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Cytochrome P450 3A4 (CYP3A4)
Main DME
DE4LYSA CP3A4_HUMAN Substrate [9]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Melanoma
ICD Disease Classification 2C30
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
Serine/threonine-protein kinase B-raf (BRAF) DTT BRAF 3.00E-01 0.1 0.2
P-glycoprotein 1 (ABCB1) DTP P-GP 9.48E-02 1.45E-01 2.92E-01
Organic anion transporting polypeptide 1B3 (SLCO1B3) DTP OATP1B3 7.57E-04 7.55E-03 3.42E-02
Organic anion transporting polypeptide 1B1 (SLCO1B1) DTP OATP1B1 5.98E-03 9.85E-03 5.46E-02
Cytochrome P450 3A4 (CYP3A4) DME CYP3A4 1.75E-01 3.78E-02 1.44E-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 Same Disease as Vemurafenib
DDI Drug Name DDI Drug ID Severity Mechanism Disease REF
Arry-162 DM1P6FR Moderate Decreased clearance of Vemurafenib due to the transporter inhibition by Arry-162. Melanoma [2C30] [48]
Selumetinib DMC7W6R Moderate Increased metabolism of Vemurafenib caused by Selumetinib mediated induction of CYP450 enzyme. Melanoma [2C30] [49]
Dabrafenib DMX6OE3 Moderate Increased metabolism of Vemurafenib caused by Dabrafenib mediated induction of CYP450 enzyme. Melanoma [2C30] [50]
Coadministration of a Drug Treating the Disease Different from Vemurafenib (Comorbidity)
DDI Drug Name DDI Drug ID Severity Mechanism Comorbidity REF
Remdesivir DMBFZ6L Moderate Increased risk of hepatotoxicity by the combination of Vemurafenib and Remdesivir. 1D6YCoronavirus Disease 2019 [1D6YCoronavirus Disease 2019] [48]
Metreleptin DM1NOEK Moderate Increased metabolism of Vemurafenib caused by Metreleptin mediated induction of CYP450 enzyme. Acute diabete complication [5A2Y] [51]
Ivosidenib DM8S6T7 Major Increased risk of prolong QT interval by the combination of Vemurafenib and Ivosidenib. Acute myeloid leukaemia [2A60] [52]
Arn-509 DMT81LZ Major Increased metabolism of Vemurafenib caused by Arn-509 mediated induction of CYP450 enzyme. Acute myeloid leukaemia [2A60] [48]
Gilteritinib DMWQ4MZ Major Increased risk of prolong QT interval by the combination of Vemurafenib and Gilteritinib. Acute myeloid leukaemia [2A60] [52]
Oliceridine DM6MDCF Major Increased risk of prolong QT interval by the combination of Vemurafenib and Oliceridine. Acute pain [MG31] [52]
Ivabradine DM0L594 Major Increased risk of ventricular arrhythmias by the combination of Vemurafenib and Ivabradine. Angina pectoris [BA40] [50]
Bedaquiline DM3906J Major Increased risk of prolong QT interval by the combination of Vemurafenib and Bedaquiline. Antimicrobial drug resistance [MG50-MG52] [52]
Levalbuterol DM5YBO1 Moderate Increased risk of ventricular arrhythmias by the combination of Vemurafenib and Levalbuterol. Asthma [CA23] [53]
Troleandomycin DMUZNIG Moderate Decreased metabolism of Vemurafenib caused by Troleandomycin mediated inhibition of CYP450 enzyme. Bacterial infection [1A00-1C4Z] [51]
Ag-221 DMS0ZBI Moderate Decreased clearance of Vemurafenib due to the transporter inhibition by Ag-221. BCR-ABL1-negative chronic myeloid leukaemia [2A41] [48]
Erdafitinib DMI782S Moderate Decreased clearance of Vemurafenib due to the transporter inhibition by Erdafitinib. Bladder cancer [2C94] [54]
Pexidartinib DMS2J0Z Major Increased risk of hepatotoxicity by the combination of Vemurafenib and Pexidartinib. Bone/articular cartilage neoplasm [2F7B] [55]
Talazoparib DM1KS78 Moderate Decreased clearance of Vemurafenib due to the transporter inhibition by Talazoparib. Breast cancer [2C60-2C6Y] [56]
LY2835219 DM93VBZ Moderate Increased metabolism of Vemurafenib caused by LY2835219 mediated induction of CYP450 enzyme. Breast cancer [2C60-2C6Y] [57]
Esterified estrogens DM9KZDO Moderate Increased metabolism of Vemurafenib caused by Esterified estrogens mediated induction of CYP450 enzyme. Breast cancer [2C60-2C6Y] [58]
Tucatinib DMBESUA Moderate Decreased metabolism of Vemurafenib caused by Tucatinib mediated inhibition of CYP450 enzyme. Breast cancer [2C60-2C6Y] [51]
Palbociclib DMD7L94 Moderate Increased metabolism of Vemurafenib caused by Palbociclib mediated induction of CYP450 enzyme. Breast cancer [2C60-2C6Y] [48]
Alpelisib DMEXMYK Moderate Increased metabolism of Vemurafenib caused by Alpelisib mediated induction of CYP450 enzyme. Breast cancer [2C60-2C6Y] [59]
Macitentan DMP79A1 Moderate Increased metabolism of Vemurafenib caused by Macitentan mediated induction of CYP450 enzyme. Cardiovascular disease [BA00-BE2Z] [60]
PF-04449913 DMSB068 Major Increased risk of prolong QT interval by the combination of Vemurafenib and PF-04449913. Chronic myelomonocytic leukaemia [2A40] [52]
Olodaterol DM62B78 Moderate Increased risk of ventricular arrhythmias by the combination of Vemurafenib and Olodaterol. Chronic obstructive pulmonary disease [CA22] [61]
Vilanterol DMF5EK1 Moderate Increased risk of ventricular arrhythmias by the combination of Vemurafenib and Vilanterol. Chronic obstructive pulmonary disease [CA22] [53]
Levonorgestrel DM1DP7T Moderate Increased metabolism of Vemurafenib caused by Levonorgestrel mediated induction of CYP450 enzyme. Contraceptive management [QA21] [58]
Osilodrostat DMIJC9X Major Increased risk of prolong QT interval by the combination of Vemurafenib and Osilodrostat. Cushing syndrome [5A70] [52]
Lumacaftor DMCLWDJ Major Increased metabolism of Vemurafenib caused by Lumacaftor mediated induction of CYP450 enzyme. Cystic fibrosis [CA25] [48]
Vortioxetine DM6F1PU Moderate Increased metabolism of Vemurafenib caused by Vortioxetine mediated induction of CYP450 enzyme. Depression [6A70-6A7Z] [62]
Deutetrabenazine DMUPFLI Major Increased risk of prolong QT interval by the combination of Vemurafenib and Deutetrabenazine. Dystonic disorder [8A02] [52]
Ingrezza DMVPLNC Major Increased risk of prolong QT interval by the combination of Vemurafenib and Ingrezza. Dystonic disorder [8A02] [52]
Stiripentol DMMSDOY Moderate Decreased metabolism of Vemurafenib caused by Stiripentol mediated inhibition of CYP450 enzyme. Epilepsy/seizure [8A61-8A6Z] [50]
Eslicarbazepine DMZREFQ Moderate Increased metabolism of Vemurafenib caused by Eslicarbazepine mediated induction of CYP450 enzyme. Epilepsy/seizure [8A61-8A6Z] [51]
Cannabidiol DM0659E Moderate Increased risk of hepatotoxicity by the combination of Vemurafenib and Cannabidiol. Epileptic encephalopathy [8A62] [50]
Bay 80-6946 DMLOS5R Moderate Increased metabolism of Vemurafenib caused by Bay 80-6946 mediated induction of CYP450 enzyme. Follicular lymphoma [2A80] [63]
Tazemetostat DMWP1BH Moderate Increased metabolism of Vemurafenib caused by Tazemetostat mediated induction of CYP450 enzyme. Follicular lymphoma [2A80] [64]
Mirabegron DMS1GYT Minor Increased metabolism of Vemurafenib caused by Mirabegron mediated induction of CYP450 enzyme. Functional bladder disorder [GC50] [65]
Ripretinib DM958QB Moderate Increased metabolism of Vemurafenib caused by Ripretinib mediated induction of CYP450 enzyme. Gastrointestinal stromal tumour [2B5B] [48]
Avapritinib DMK2GZX Moderate Increased metabolism of Vemurafenib caused by Avapritinib mediated induction of CYP450 enzyme. Gastrointestinal stromal tumour [2B5B] [50]
MK-1439 DM215WE Moderate Increased metabolism of Vemurafenib caused by MK-1439 mediated induction of CYP450 enzyme. Human immunodeficiency virus disease [1C60-1C62] [66]
Cobicistat DM6L4H2 Moderate Decreased metabolism of Vemurafenib caused by Cobicistat mediated inhibition of CYP450 enzyme. Human immunodeficiency virus disease [1C60-1C62] [51]
Dolutegravir DMCZGRE Minor Increased metabolism of Vemurafenib caused by Dolutegravir mediated induction of CYP450 enzyme. Human immunodeficiency virus disease [1C60-1C62] [67]
Elvitegravir DMG9B1U Moderate Increased metabolism of Vemurafenib caused by Elvitegravir mediated induction of CYP450 enzyme. Human immunodeficiency virus disease [1C60-1C62] [48]
Aliskiren DM1BV7W Moderate Decreased clearance of Vemurafenib due to the transporter inhibition by Aliskiren. Hypertension [BA00-BA04] [52]
Lesinurad DMUR64T Moderate Increased metabolism of Vemurafenib caused by Lesinurad mediated induction of CYP450 enzyme. Inborn purine/pyrimidine/nucleotide metabolism error [5C55] [51]
Berotralstat DMWA2DZ Major Decreased clearance of Vemurafenib due to the transporter inhibition by Berotralstat. Innate/adaptive immunodeficiency [4A00] [68]
Suvorexant DM0E6S3 Moderate Increased metabolism of Vemurafenib caused by Suvorexant mediated induction of CYP450 enzyme. Insomnia [7A00-7A0Z] [69]
Tasimelteon DMLOQ1V Moderate Decreased metabolism of Vemurafenib caused by Tasimelteon mediated inhibition of CYP450 enzyme. Insomnia [7A00-7A0Z] [70]
Polyethylene glycol DM4I1JP Moderate Increased risk of ventricular arrhythmias by the combination of Vemurafenib and Polyethylene glycol. Irritable bowel syndrome [DD91] [50]
Naloxegol DML0B41 Minor Decreased clearance of Vemurafenib due to the transporter inhibition by Naloxegol. Large intestine motility disorder [DB32] [71]
Pemigatinib DM819JF Moderate Increased metabolism of Vemurafenib caused by Pemigatinib mediated induction of CYP450 enzyme. Liver cancer [2C12] [50]
Brigatinib DM7W94S Moderate Increased metabolism of Vemurafenib caused by Brigatinib mediated induction of CYP450 enzyme. Lung cancer [2C25] [48]
Ceritinib DMB920Z Major Increased risk of prolong QT interval by the combination of Vemurafenib and Ceritinib. Lung cancer [2C25] [52]
PF-06463922 DMKM7EW Moderate Increased metabolism of Vemurafenib caused by PF-06463922 mediated induction of CYP450 enzyme. Lung cancer [2C25] [51]
Osimertinib DMRJLAT Major Increased risk of prolong QT interval by the combination of Vemurafenib and Osimertinib. Lung cancer [2C25] [52]
Capmatinib DMYCXKL Moderate Decreased clearance of Vemurafenib due to the transporter inhibition by Capmatinib. Lung cancer [2C25] [72]
Selpercatinib DMZR15V Major Increased risk of prolong QT interval by the combination of Vemurafenib and Selpercatinib. Lung cancer [2C25] [52]
Calaspargase pegol DMQZBXI Moderate Increased risk of hepatotoxicity by the combination of Vemurafenib and Calaspargase pegol. Malignant haematopoietic neoplasm [2B33] [73]
Idelalisib DM602WT Moderate Increased risk of hepatotoxicity by the combination of Vemurafenib and Idelalisib. Mature B-cell leukaemia [2A82] [74]
GDC-0199 DMH0QKA Major Decreased clearance of Vemurafenib due to the transporter inhibition by GDC-0199. Mature B-cell leukaemia [2A82] [48]
Acalabrutinib DM7GCVW Moderate Increased metabolism of Vemurafenib caused by Acalabrutinib mediated induction of CYP450 enzyme. Mature B-cell lymphoma [2A85] [75]
Ibrutinib DMHZCPO Moderate Increased metabolism of Vemurafenib caused by Ibrutinib mediated induction of CYP450 enzyme. Mature B-cell lymphoma [2A85] [76]
Ubrogepant DM749I3 Moderate Increased metabolism of Vemurafenib caused by Ubrogepant mediated induction of CYP450 enzyme. Migraine [8A80] [77]
Rimegepant DMHOAUG Moderate Decreased clearance of Vemurafenib due to the transporter inhibition by Rimegepant. Migraine [8A80] [78]
Lasmiditan DMXLVDT Moderate Decreased clearance of Vemurafenib due to the transporter inhibition by Lasmiditan. Migraine [8A80] [79]
Ozanimod DMT6AM2 Major Increased risk of prolong QT interval by the combination of Vemurafenib and Ozanimod. Multiple sclerosis [8A40] [52]
Rolapitant DM8XP26 Moderate Increased metabolism of Vemurafenib caused by Rolapitant mediated induction of CYP450 enzyme. Nausea/vomiting [MD90] [80]
E-2007 DMJDYNQ Moderate Increased metabolism of Vemurafenib caused by E-2007 mediated induction of CYP450 enzyme. Neuropathy [8C0Z] [50]
Entrectinib DMMPTLH Major Increased risk of prolong QT interval by the combination of Vemurafenib and Entrectinib. Non-small cell lung cancer [2C25] [52]
Olaparib DM8QB1D Moderate Increased metabolism of Vemurafenib caused by Olaparib mediated induction of CYP450 enzyme. Ovarian cancer [2C73] [48]
Rucaparib DM9PVX8 Major Increased risk of prolong QT interval by the combination of Vemurafenib and Rucaparib. Ovarian cancer [2C73] [52]
Triclabendazole DMPWGBR Major Increased risk of prolong QT interval by the combination of Vemurafenib and Triclabendazole. Parasitic worm infestation [1F90] [52]
Abametapir DM2RX0I Moderate Decreased metabolism of Vemurafenib caused by Abametapir mediated inhibition of CYP450 enzyme. Pediculosis [1G00] [81]
Macimorelin DMQYJIR Major Increased risk of prolong QT interval by the combination of Vemurafenib and Macimorelin. Pituitary gland disorder [5A60-5A61] [82]
Lefamulin DME6G97 Major Increased risk of prolong QT interval by the combination of Vemurafenib and Lefamulin. Pneumonia [CA40] [52]
Enzalutamide DMGL19D Major Increased metabolism of Vemurafenib caused by Enzalutamide mediated induction of CYP450 enzyme. Prostate cancer [2C82] [48]
Relugolix DMK7IWL Major Decreased metabolism of Vemurafenib caused by Relugolix mediated inhibition of CYP450 enzyme. Prostate cancer [2C82] [83]
Darolutamide DMV7YFT Moderate Decreased clearance of Vemurafenib due to the transporter inhibition by Darolutamide. Prostate cancer [2C82] [84]
Selexipag DMAHSU0 Moderate Decreased metabolism of Vemurafenib caused by Selexipag mediated inhibition of CYP450 enzyme. Pulmonary hypertension [BB01] [48]
Riociguat DMXBLMP Moderate Increased metabolism of Vemurafenib caused by Riociguat mediated induction of CYP450 enzyme. Pulmonary hypertension [BB01] [85]
Tofacitinib DMBS370 Moderate Increased metabolism of Vemurafenib caused by Tofacitinib mediated induction of CYP450 enzyme. Rheumatoid arthritis [FA20] [48]
Tedizolid DMG2SKR Moderate Decreased clearance of Vemurafenib due to the transporter inhibition by Tedizolid. Skin and skin-structure infection [1F28-1G0Z] [50]
LDE225 DMM9F25 Moderate Increased metabolism of Vemurafenib caused by LDE225 mediated induction of CYP450 enzyme. Skin cancer [2C30-2C37] [86]
Telotristat ethyl DMDIYFZ Moderate Increased metabolism of Vemurafenib caused by Telotristat ethyl mediated induction of CYP450 enzyme. Small intestine developmental anomaly [DA90] [87]
Larotrectinib DM26CQR Moderate Decreased clearance of Vemurafenib due to the transporter inhibition by Larotrectinib. Solid tumour/cancer [2A00-2F9Z] [48]
LEE011 DMMX75K Major Increased risk of prolong QT interval by the combination of Vemurafenib and LEE011. Solid tumour/cancer [2A00-2F9Z] [52]
Pitolisant DM8RFNJ Major Increased risk of prolong QT interval by the combination of Vemurafenib and Pitolisant. Somnolence [MG42] [52]
Pomalidomide DMTGBAX Moderate Decreased metabolism of Vemurafenib caused by Pomalidomide mediated inhibition of CYP450 enzyme. Systemic sclerosis [4A42] [51]
Fostamatinib DM6AUHV Moderate Increased metabolism of Vemurafenib caused by Fostamatinib mediated induction of CYP450 enzyme. Thrombocytopenia [3B64] [88]
Lusutrombopag DMH6IKO Moderate Decreased clearance of Vemurafenib due to the transporter inhibition by Lusutrombopag. Thrombocytopenia [3B64] [89]
Lenvatinib DMB1IU4 Major Increased risk of prolong QT interval by the combination of Vemurafenib and Lenvatinib. Thyroid cancer [2D10] [52]
Linagliptin DMWFJTR Moderate Increased metabolism of Vemurafenib caused by Linagliptin mediated induction of CYP450 enzyme. Type 2 diabetes mellitus [5A11] [90]
Elagolix DMB2C0E Moderate Increased metabolism of Vemurafenib caused by Elagolix mediated induction of CYP450 enzyme. Uterine fibroid [2E86] [91]
⏷ Show the Full List of 91 DDI Information of This Drug

Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG
DIG Name DIG ID PubChem CID Functional Classification
Carmellose sodium E00625 Not Available Disintegrant
Eisenoxyd E00585 56841934 Colorant
Polyethylene glycol 3350 E00652 Not Available Coating agent; Diluent; Ointment base; Plasticizing agent; Solvent; Suppository base; lubricant
Talc E00520 16211421 Anticaking agent; Diluent; Glidant; lubricant
Titanium dioxide E00322 26042 Coating agent; Colorant; Opacifying agent
Pharmaceutical Formulation
Formulation Name Drug Dosage Dosage Form Route
Vemurafenib 240 mg tablet 240 mg Oral Tablet Oral
Jump to Detail Pharmaceutical Formulation Page 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: 5893).
2 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
3 ClinicalTrials.gov (NCT01898585) An Open-Label Study of Zelboraf (Vemurafenib) in Patients With Braf V600 Mutation Positive Metastatic Melanoma. U.S. National Institutes of Health.
4 Zhang W, Heinzmann D, Grippo JF: Clinical Pharmacokinetics of Vemurafenib. Clin Pharmacokinet. 2017 Mar 2. doi: 10.1007/s40262-017-0523-7.
5 BDDCS predictions, self-correcting aspects of BDDCS assignments, BDDCS assignment corrections, and classification for more than 175 additional drugs
6 A single-dose mass balance and metabolite-profiling study of vemurafenib in patients with metastatic melanoma. Pharmacol Res Perspect. 2015 Mar;3(2):e00113. doi: 10.1002/prp2.113.
7 Contribution of OATP1B1 and OATP1B3 to the disposition of sorafenib and sorafenib-glucuronide. Clin Cancer Res. 2013 Mar 15;19(6):1458-66.
8 Differential effects of the oncogenic BRAF inhibitor PLX4032 (vemurafenib) and its progenitor PLX4720 on ABCB1 function. J Pharm Pharm Sci. 2014;17(1):154-68.
9 Vemurafenib for the treatment of melanoma. Expert Opin Pharmacother. 2012 Dec;13(17):2533-43.
10 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.
11 Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47.
12 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.
13 Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
14 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.
15 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.
16 Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
17 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.
18 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.
19 Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
20 MDR1 (ABCB1) G1199A (Ser400Asn) polymorphism alters transepithelial permeability and sensitivity to anticancer agents. Cancer Chemother Pharmacol. 2009 Jun;64(1):183-8.
21 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.
22 Folate transporter expression decreases in the human placenta throughout pregnancy and in pre-eclampsia. Pregnancy Hypertens. 2012 Apr;2(2):123-31.
23 Comparative studies on in vitro methods for evaluating in vivo function of MDR1 P-glycoprotein. Pharm Res. 2001 Dec;18(12):1660-8.
24 Antiestrogens and steroid hormones: substrates of the human P-glycoprotein. Biochem Pharmacol. 1994 Jul 19;48(2):287-92.
25 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.
26 Preclinical Mouse Models To Study Human OATP1B1- and OATP1B3-Mediated Drug-Drug Interactions in Vivo. Mol Pharm. 2015 Dec 7;12(12):4259-69.
27 Organic anion transporting polypeptide 1B1: a genetically polymorphic transporter of major importance for hepatic drug uptake. Pharmacol Rev. 2011 Mar;63(1):157-81.
28 Identification of drugs and drug metabolites as substrates of multidrug resistance protein 2 (MRP2) using triple-transfected MDCK-OATP1B1-UGT1A1-MRP2 cells. Br J Pharmacol. 2012 Mar;165(6):1836-1847.
29 The effect of SLCO1B1*15 on the disposition of pravastatin and pitavastatin is substrate dependent: the contribution of transporting activity changes by SLCO1B1*15. Pharmacogenet Genomics. 2008 May;18(5):424-33.
30 Influence of SLCO1B1, 1B3, 2B1 and ABCC2 genetic polymorphisms on mycophenolic acid pharmacokinetics in Japanese renal transplant recipients. Eur J Clin Pharmacol. 2007 Dec;63(12):1161-9.
31 Rifampicin alters atorvastatin plasma concentration on the basis of SLCO1B1 521T>C polymorphism. Clin Chim Acta. 2009 Jul;405(1-2):49-52.
32 FDA Drug Development and Drug Interactions
33 LST-2, a human liver-specific organic anion transporter, determines methotrexate sensitivity in gastrointestinal cancers. Gastroenterology. 2001 Jun;120(7):1689-99.
34 Effect of pregnane X receptor ligands on transport mediated by human OATP1B1 and OATP1B3. Eur J Pharmacol. 2008 Apr 14;584(1):57-65.
35 Influence of non-steroidal anti-inflammatory drugs on organic anion transporting polypeptide (OATP) 1B1- and OATP1B3-mediated drug transport. Drug Metab Dispos. 2011 Jun;39(6):1047-53.
36 Relevance of conserved lysine and arginine residues in transmembrane helices for the transport activity of organic anion transporting polypeptide 1B3. Br J Pharmacol. 2010 Feb 1;159(3):698-708.
37 Impact of OATP transporters on pharmacokinetics. Br J Pharmacol. 2009 Oct;158(3):693-705.
38 Clinical pipeline report, company report or official report of GlaxoSmithKline (2011).
39 Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
40 Identification of PLX4032-resistance mechanisms and implications for novel RAF inhibitors. Pigment Cell Melanoma Res. 2014 Mar;27(2):253-62.
41 Clinical pipeline report, company report or official report of Ambit Biosciences.
42 BGB-283, a Novel RAF Kinase and EGFR Inhibitor, Displays Potent Antitumor Activity in BRAF-Mutated Colorectal Cancers. Mol Cancer Ther. 2015 Oct;14(10):2187-97.
43 National Cancer Institute Drug Dictionary (drug id 688029).
44 National Cancer Institute Drug Dictionary (drug id 680347).
45 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
46 Clinical pipeline report, company report or official report of Exelixis (2011).
47 Clinical pipeline report, company report or official report of ABM Therapeutics.
48 Cerner Multum, Inc. "Australian Product Information.".
49 Product Information. Koselugo (selumetinib). Astra-Zeneca Pharmaceuticals, Wilmington, DE.
50 Cerner Multum, Inc. "UK Summary of Product Characteristics.".
51 Product Information. Zelboraf (vemurafenib). Genentech, South San Francisco, CA.
52 Canadian Pharmacists Association.
53 Product Information. Arcapta Neohaler (indacaterol). Novartis Pharmaceuticals, East Hanover, NJ.
54 Product Information. Balversa (erdafitinib). Janssen Products, LP, Horsham, PA.
55 Product Information. Turalio (pexidartinib). Daiichi Sankyo, Inc., Parsippany, NJ.
56 Product Information. Talzenna (talazoparib). Pfizer U.S. Pharmaceuticals Group, New York, NY.
57 Product Information. Verzenio (abemaciclib). Lilly, Eli and Company, Indianapolis, IN.
58 Baciewicz AM "Oral contraceptive drug interactions." Ther Drug Monit 7 (1985): 26-35. [PMID: 2859674]
59 Product Information. Piqray (alpelisib). Novartis Pharmaceuticals, East Hanover, NJ.
60 Bruderer S, Aanismaa P, Homery MC, et al. "Effect of cyclosporine and rifampin on the pharmacokinetics of macitentan, a tissue-targeting dual endothelin receptor antagonist." AAPS J 14 (2012): 68-78. [PMID: 22189899]
61 Bengtsson B, Fagerstrom PO "Extrapulmonary effects of terbutaline during prolonged administration." Clin Pharmacol Ther 31 (1982): 726-32. [PMID: 7042176]
62 Product Information. Brintellix (vortioxetine). Takeda Pharmaceuticals America, Lincolnshire, IL.
63 Product Information. Aliqopa (copanlisib). Bayer Pharmaceutical Inc, West Haven, CT.
64 Product Information. Tazverik (tazemetostat). Epizyme, Inc, Cambridge, MA.
65 Product Information. Myrbetriq (mirabegron). Astellas Pharma US, Inc, Deerfield, IL.
66 Product Information. Pifeltro (doravirine). Merck & Company Inc, Whitehouse Station, NJ.
67 Product Information. Tivicay (dolutegravir). ViiV Healthcare, Research Triangle Park, NC.
68 Product Information. Orladeyo (berotralstat). BioCryst Pharmaceuticals Inc, Durham, NC.
69 Product Information. Belsomra (suvorexant). Merck & Company Inc, Whitehouse Station, NJ.
70 Product Information. Hetlioz (tasimelteon). Vanda Pharmaceuticals Inc, Rockville, MD.
71 Product Information. Movantik (naloxegol). Astra-Zeneca Pharmaceuticals, Wilmington, DE.
72 Product Information. Tabrecta (capmatinib). Novartis Pharmaceuticals, East Hanover, NJ.
73 Al-Nawakil C, Willems L, Mauprivez C, et.al "Successful treatment of l-asparaginase-induced severe acute hepatotoxicity using mitochondrial cofactors." Leuk Lymphoma 55 (2014): 1670-4. [PMID: 24090500]
74 Product Information. Zydelig (idelalisib). Gilead Sciences, Foster City, CA.
75 Product Information. Calquence (acalabrutinib). Astra-Zeneca Pharmaceuticals, Wilmington, DE.
76 Product Information. Imbruvica (ibrutinib). Pharmacyclics Inc, Sunnyvale, CA.
77 Product Information. Ubrelvy (ubrogepant). Allergan Inc, Irvine, CA.
78 Product Information. Nurtec ODT (rimegepant). Biohaven Pharmaceuticals, New Haven, CT.
79 Product Information. Reyvow (lasmiditan). Lilly, Eli and Company, Indianapolis, IN.
80 Product Information. Varubi (rolapitant). Tesaro Inc., Waltham, MA.
81 Product Information. Xeglyze (abametapir topical). Dr. Reddy's Laboratories Inc, Upper Saddle River, NJ.
82 Product Information. Macrilen (macimorelin). Aeterna Zentaris, Charleston, SC.
83 Product Information. Orgovyx (relugolix). Myovant Sciences, Inc., Brisbane, CA.
84 Product Information. Nubeqa (darolutamide). Bayer HealthCare Pharmaceuticals Inc., Whippany, NJ.
85 Product Information. Adempas (riociguat). Bayer Pharmaceutical Inc, West Haven, CT.
86 Product Information. Odomzo (sonidegib). Novartis Pharmaceuticals, East Hanover, NJ.
87 Product Information. Diabinese (chlorpropamide). Pfizer US Pharmaceuticals, New York, NY.
88 Product Information. Tavalisse (fostamatinib). Rigel Pharmaceuticals, South San Francisco, CA.
89 EMA. European Medicines Agency. European Union "EMA - List of medicines under additional monitoring.".
90 Product Information. Tradjenta (linagliptin). Boehringer Ingelheim, Ridgefield, CT.
91 Product Information. Orilissa (elagolix). AbbVie US LLC, North Chicago, IL.