Details of the Drug

General Information of Drug (ID: DMMIQ7G)

Drug Name
Rosuvastatin
Synonyms
Astende; Cirantan; Cresadex; Creston; Crestor; Provisacor; Razel; Rosedex; Rosimol; Rosumed; Rosustatin; Rosuvas; Rosuvast; Rosvel; Rovartal; Simestat; Sinlip; Vivacor; Rosuvastatin [INN]; Rosuvastatin calcium; Rosuvastatin calcium [USAN]; Rosuvastatin hemicalcium; S 4522; ZD 4522; ZD4522; AZD-4522; Creston (TN);Crestor (TN); Pyrimidine Compound, 26; Rosuvastatin (INN); S-4522; ZD 4522, calcium salt; ZD-4522; Rosuvastatin calcium (JAN/USAN); Bis[(E)-7-[4-(4-fluorophenyl)-6-isopropyl-2-[methyl(methylsulfonyl)amino] pyrimidin-5-yl](3R,5S)-3,5-dihydroxyhelpt-6-enoic acid] calcium salt; Calcium (E,3R,5S)-7-[4-(4-fluorophenyl)-2-[methyl(methylsulfonyl)amino]-6-propan-2-ylpyrimidin-5-yl]-3,5-dihydroxyhept-6-enoate; (3R,5S,6E)-7-(4-(4-fluorophenyl)-6-(1-methylethyl)-2-(ethyl(methylsulfonyl)amino)-5-pyrimidinyl)-3,5-dihydroxy-6-heptenoic acid; (3R,5S,6E)-7-{4-(4-fluorophenyl)-2-[methyl(methylsulfonyl)amino]-6-(propan-2-yl)pyrimidin-5-yl}-3,5-dihydroxyhept-6-enoic acid; (3R,5S,6E)-7-{4-(4-fluorophenyl)-6-isopropyl-2-[methyl(methylsulfonyl)amino]pyrimidin-5-yl}-3,5-dihydroxyhept-6-enoic acid; (E,3R,5R)-7-[4-(4-fluorophenyl)-2-[methyl(methylsulfonyl)amino]-6-propan-2-ylpyrimidin-5-yl]-3,5-dihydroxyhept-6-enoic acid; (E,3R,5S)-7-[4-(4-fluorophenyl)-2-[methyl(methylsulfonyl)amino]-6-propan-2-ylpyrimidin-5-yl]-3,5-dihydroxyhept-6-enoic acid; (S-((R*,S*-(E)))-7-(4-(4-fluorophenyl)-6-(1-methylethyl)-2-(methyl(methylsulfonyl) amino)-5-pyrimidinyl)-3,5-dihydroxy-6-heptenoic acid, calcium salt (2:1); (S-(R*,S*-(E)))-7-(4-(4-Fluorophenyl)-6-(1-methylethyl)-2-(methyl(methylsulfonyl)amino)-5-pyrimidinyl)-3,5-dihydroxy-6-heptenoic acid, calcium salt (2:1); 6-Heptenoic acid, 7-(4-(4-fluorophenyl)-6-(1-methylethyl)-2-(ethyl(methylsulfonyl)amino)-5-pyrimidinyl)-3,5-dihydroxy-, (3R,5S,6E); 6-Heptenoic acid, 7-(4-(4-fluorophenyl)-6-(1-methylethyl)-2-(methyl(methylsulfonyl)amino)-5-pyrimidinyl)-3,5-dihydroxy-, calcium salt (2:1), (3R,5S,6E)
Indication
Disease Entry ICD 11 Status REF
Hypercholesterolaemia 5C80.0 Approved [1], [2]
Elevated C-reactive protein MA14.15 Phase 3 [1], [2]
Therapeutic Class
Anticholesteremic Agents
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 481.5
Topological Polar Surface Area (xlogp) 1.6
Rotatable Bond Count (rotbonds) 10
Hydrogen Bond Donor Count (hbonddonor) 3
Hydrogen Bond Acceptor Count (hbondacc) 10
ADMET Property
Absorption Cmax
The maximum plasma concentration (Cmax) of drug is 6.06 mcg/L [3]
Absorption Tmax
The time to maximum plasma concentration (Tmax) is 5 h [3]
BDDCS Class
Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 3: high solubility and low permeability [4]
Bioavailability
The bioavailability of drug is 20% [3]
Clearance
The drug present in the plasma can be removed from the body at the rate of 11 mL/min/kg [5]
Elimination
Rosuvastatin is not extensively metabolized; approximately 10% of a radiolabeled dose is recovered as metabolite [3]
Half-life
The concentration or amount of drug in body reduced by one-half in 19 hours [6]
MRTD
The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 1.18665 micromolar/kg/day [7]
Unbound Fraction
The unbound fraction of drug in plasma is 0.12% [5]
Vd
The volume of distribution (Vd) of drug is 134 L [8]
Chemical Identifiers
Formula
C22H28FN3O6S
IUPAC Name
(E,3R,5S)-7-[4-(4-fluorophenyl)-2-[methyl(methylsulfonyl)amino]-6-propan-2-ylpyrimidin-5-yl]-3,5-dihydroxyhept-6-enoic acid
Canonical SMILES
CC(C)C1=NC(=NC(=C1/C=C/[C@H](C[C@H](CC(=O)O)O)O)C2=CC=C(C=C2)F)N(C)S(=O)(=O)C
InChI
InChI=1S/C22H28FN3O6S/c1-13(2)20-18(10-9-16(27)11-17(28)12-19(29)30)21(14-5-7-15(23)8-6-14)25-22(24-20)26(3)33(4,31)32/h5-10,13,16-17,27-28H,11-12H2,1-4H3,(H,29,30)/b10-9+/t16-,17-/m1/s1
InChIKey
BPRHUIZQVSMCRT-VEUZHWNKSA-N
Cross-matching ID
PubChem CID
446157
ChEBI ID
CHEBI:38545
CAS Number
287714-41-4
DrugBank ID
DB01098
TTD ID
D0JE2E
VARIDT ID
DR00223
INTEDE ID
DR1445
ACDINA ID
D00608

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
HMG-CoA reductase (HMGCR) TTPADOQ HMDH_HUMAN Inhibitor [9]

Drug Transporter (DTP)
DTP Name DTP ID UniProt ID MOA REF
Sodium/taurocholate cotransporting polypeptide (SLC10A1) DT56EKP NTCP_HUMAN Substrate [10]
Multidrug resistance-associated protein 2 (ABCC2) DTFI42L MRP2_HUMAN Substrate [11]
Organic anion transporting polypeptide 2B1 (SLCO2B1) DTPFTEQ SO2B1_HUMAN Substrate [11]
Organic anion transporting polypeptide 1A2 (SLCO1A2) DTE2B1D SO1A2_HUMAN Substrate [10]
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [11]
Organic anion transporting polypeptide 1B1 (SLCO1B1) DT3D8F0 SO1B1_HUMAN Substrate [11]
Organic anion transporting polypeptide 1B3 (SLCO1B3) DT9C1TS SO1B3_HUMAN Substrate [11]
Organic anion transporter 3 (SLC22A8) DTVP67E S22A8_HUMAN Substrate [12]
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) DE4LYSA CP3A4_HUMAN Substrate [13]
Cytochrome P450 2C9 (CYP2C9)
Main DME 		DE5IED8 CP2C9_HUMAN Substrate [13]
Cytochrome P450 1B1 (CYP1B1) DE9QHP6 CP1B1_HUMAN Substrate [14]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Hypercholesterolaemia
ICD Disease Classification 5C80.0
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
HMG-CoA reductase (HMGCR) DTT HMGCR 1.01E-05 0.65 1.53
Organic anion transporter 3 (SLC22A8) DTP OAT3 1.54E-03 -5.09E-01 -1.49E+00
P-glycoprotein 1 (ABCB1) DTP P-GP 3.29E-14 -7.08E-01 -1.99E+00
Organic anion transporting polypeptide 2B1 (SLCO2B1) DTP OATP2B1 3.80E-01 -1.23E-02 -5.33E-02
Breast cancer resistance protein (ABCG2) DTP BCRP 2.28E-08 -3.66E-01 -8.07E-01
Multidrug resistance-associated protein 2 (ABCC2) DTP MRP2 4.30E-02 -2.29E-01 -9.10E-01
Organic anion transporting polypeptide 1A2 (SLCO1A2) DTP OATP1A2 7.28E-02 -7.13E-02 -4.55E-01
Organic anion transporting polypeptide 1B3 (SLCO1B3) DTP OATP1B3 1.65E-01 -6.07E-02 -3.77E-01
Sodium/taurocholate cotransporting polypeptide (SLC10A1) DTP NTCP 7.48E-02 -5.70E-02 -2.14E-01
Organic anion transporting polypeptide 1B1 (SLCO1B1) DTP OATP1B1 3.27E-01 -5.78E-02 -3.84E-01
Cytochrome P450 1B1 (CYP1B1) DME CYP1B1 1.27E-09 2.24E+00 2.07E+00
Cytochrome P450 2C9 (CYP2C9) DME CYP2C9 2.63E-03 -1.18E-01 -3.80E-01
Cytochrome P450 3A4 (CYP3A4) DME CYP3A4 3.24E-05 -3.48E-01 -1.34E+00
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 Rosuvastatin
DDI Drug Name DDI Drug ID Severity Mechanism Disease REF
Bempedoic acid DM1CI9R Moderate Decreased clearance of Rosuvastatin due to the transporter inhibition by Bempedoic acid. Hyper-lipoproteinaemia [5C80] [121]
Gemfibrozil DMD8Q3J Major Decreased clearance of Rosuvastatin due to the transporter inhibition by Gemfibrozil. Hyper-lipoproteinaemia [5C80] [122]
Mipomersen DMGSRN1 Major Increased risk of hepatotoxicity by the combination of Rosuvastatin and Mipomersen. Hyper-lipoproteinaemia [5C80] [123]
Teriflunomide DMQ2FKJ Major Increased risk of hepatotoxicity by the combination of Rosuvastatin and Teriflunomide. Hyper-lipoproteinaemia [5C80] [124]
BMS-201038 DMQTAGO Major Increased risk of hepatotoxicity by the combination of Rosuvastatin and BMS-201038. Hyper-lipoproteinaemia [5C80] [125]
Coadministration of a Drug Treating the Disease Different from Rosuvastatin (Comorbidity)
DDI Drug Name DDI Drug ID Severity Mechanism Comorbidity REF
Remdesivir DMBFZ6L Moderate Increased risk of hepatotoxicity by the combination of Rosuvastatin and Remdesivir. 1D6YCoronavirus Disease 2019 [1D6YCoronavirus Disease 2019] [124]
Midostaurin DMI6E0R Moderate Decreased clearance of Rosuvastatin due to the transporter inhibition by Midostaurin. Acute myeloid leukaemia [2A60] [126]
Arn-509 DMT81LZ Moderate Accelerated clearance of Rosuvastatin due to the transporter induction by Arn-509. Acute myeloid leukaemia [2A60] [126]
Ag-221 DMS0ZBI Major Decreased clearance of Rosuvastatin due to the transporter inhibition by Ag-221. BCR-ABL1-negative chronic myeloid leukaemia [2A41] [124]
Alpelisib DMEXMYK Moderate Increased metabolism of Rosuvastatin caused by Alpelisib mediated induction of CYP450 enzyme. Breast cancer [2C60-2C6Y] [127]
PF-04449913 DMSB068 Moderate Decreased clearance of Rosuvastatin due to the transporter inhibition by PF-04449913. Chronic myelomonocytic leukaemia [2A40] [126]
MK-8228 DMOB58Q Moderate Decreased clearance of Rosuvastatin due to the transporter inhibition by MK-8228. Cytomegaloviral disease [1D82] [128]
SODIUM CITRATE DMHPD2Y Moderate Decreased absorption of Rosuvastatin due to altered gastric pH caused by SODIUM CITRATE. Discovery agent [N.A.] [122]
Eslicarbazepine DMZREFQ Moderate Increased metabolism of Rosuvastatin caused by Eslicarbazepine mediated induction of UGT. Epilepsy/seizure [8A61-8A6Z] [126]
Simeprevir DMLUA9D Major Decreased clearance of Rosuvastatin due to the transporter inhibition by Simeprevir. Hepatitis virus infection [1E50-1E51] [129]
GS-9857 DMYU6P5 Major Decreased clearance of Rosuvastatin due to the transporter inhibition by GS-9857. Hepatitis virus infection [1E50-1E51] [130]
Brentuximab vedotin DMWLC57 Moderate Increased risk of hepatotoxicity by the combination of Rosuvastatin and Brentuximab vedotin. Hodgkin lymphoma [2B30] [131]
Fostemsavir DM50ILT Moderate Decreased clearance of Rosuvastatin due to the transporter inhibition by Fostemsavir. Human immunodeficiency virus disease [1C60-1C62] [132]
Cobicistat DM6L4H2 Moderate Decreased clearance of Rosuvastatin due to the transporter inhibition by Cobicistat. Human immunodeficiency virus disease [1C60-1C62] [126]
Lopinavir DMITQS0 Major Decreased clearance of Rosuvastatin due to the transporter inhibition by Lopinavir. Human immunodeficiency virus disease [1C60-1C62] [133]
Darunavir DMN3GCH Major Decreased clearance of Rosuvastatin due to the transporter inhibition by Darunavir. Human immunodeficiency virus disease [1C60-1C62] [124]
PF-06463922 DMKM7EW Moderate Increased metabolism of Rosuvastatin caused by PF-06463922 mediated induction of CYP450 enzyme. Lung cancer [2C25] [124]
Capmatinib DMYCXKL Moderate Decreased clearance of Rosuvastatin due to the transporter inhibition by Capmatinib. Lung cancer [2C25] [134]
Idelalisib DM602WT Moderate Increased risk of hepatotoxicity by the combination of Rosuvastatin and Idelalisib. Mature B-cell leukaemia [2A82] [135]
Dabrafenib DMX6OE3 Moderate Decreased clearance of Rosuvastatin due to the transporter inhibition by Dabrafenib. Melanoma [2C30] [124]
Lasmiditan DMXLVDT Moderate Decreased clearance of Rosuvastatin due to the transporter inhibition by Lasmiditan. Migraine [8A80] [136]
Rolapitant DM8XP26 Moderate Decreased clearance of Rosuvastatin due to the transporter inhibition by Rolapitant. Nausea/vomiting [MD90] [137]
Olaparib DM8QB1D Moderate Decreased clearance of Rosuvastatin due to the transporter inhibition by Olaparib. Ovarian cancer [2C73] [124]
Tedizolid DMG2SKR Moderate Decreased clearance of Rosuvastatin due to the transporter inhibition by Tedizolid. Skin and skin-structure infection [1F28-1G0Z] [126]
⏷ Show the Full List of 24 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
Allura red AC dye E00338 33258 Colorant
Butylated hydroxytoluene E00336 31404 Antioxidant
FD&C blue no. 1 E00263 19700 Colorant
FD&C blue no. 2 E00446 2723854 Colorant
Hydrazine yellow E00409 164825 Colorant
Mannitol E00103 6251 Diluent; Flavoring agent; Lyophilization aid; Plasticizing agent; Tonicity agent
Meglumine E00181 8567 Buffering agent
Quinoline yellow WS E00309 24671 Colorant
Sodium citrate anhydrous E00102 6224 Alkalizing agent; Buffering agent; Complexing agent; Emulsifying agent
Sodium lauryl sulfate E00464 3423265 Emulsifying agent; Modified-release agent; Penetration agent; Solubilizing agent; Surfactant; lubricant
Sodium stearyl fumarate E00545 23665634 lubricant
Sunset yellow FCF E00255 17730 Colorant
Beta-D-lactose E00099 6134 Diluent; Dry powder inhaler carrier; Lyophilization aid
Brushite E00392 104805 Diluent
Butylhydroxyanisole E00308 24667 Antimicrobial preservative; Antioxidant
Calcium hydrogenphosphate E00294 24441 Diluent
Crospovidone E00626 Not Available Disintegrant
Eisenoxyd E00585 56841934 Colorant
Ferric hydroxide oxide yellow E00539 23320441 Colorant
Hypromellose E00634 Not Available Coating agent
Lactose monohydrate E00393 104938 Binding agent; Diluent; Dry powder inhaler carrier; Lyophilization aid
Magnesium oxide E00232 14792 Anticaking agent; Diluent; Emulsifying agent; Glidant; Tonicity agent
Magnesium stearate E00208 11177 lubricant
Polyethylene glycol 3350 E00652 Not Available Coating agent; Diluent; Ointment base; Plasticizing agent; Solvent; Suppository base; lubricant
Polyethylene glycol 4000 E00654 Not Available Coating agent; Diluent; Ointment base; Plasticizing agent; Solvent; Suppository base; lubricant
Polyethylene glycol 6000 E00655 Not Available Coating agent; Diluent; Ointment base; Plasticizing agent; Solvent; Suppository base; lubricant
Silicon dioxide E00670 Not Available Anticaking agent; Opacifying agent; Viscosity-controlling agent
Sodium bicarbonate E00424 516892 Alkalizing agent; Diluent
Sodium carbonate monohydrate E00454 2735133 Alkalizing agent; Buffering agent; Diluent; Dispersing agent
Talc E00520 16211421 Anticaking agent; Diluent; Glidant; lubricant
Titanium dioxide E00322 26042 Coating agent; Colorant; Opacifying agent
Triacetin E00080 5541 Humectant; Plasticizing agent; Solvent
Vinylpyrrolidone E00668 Not Available Binding agent; Coating agent; Disintegrant; Film/membrane-forming agent; Solubilizing agent; Suspending agent
⏷ Show the Full List of 33 Pharmaceutical Excipients of This Drug
Pharmaceutical Formulation
Formulation Name Drug Dosage Dosage Form Route
Rosuvastatin 10 mg tablet 10 mg Oral Tablet Oral
Rosuvastatin 20 mg tablet 20 mg Oral Tablet Oral
Rosuvastatin 40 mg tablet 40 mg Oral Tablet Oral
Rosuvastatin 5 mg tablet 5 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: 2954).
2 Emerging drugs for acute and chronic heart failure: current and future developments. Expert Opin Emerg Drugs. 2007 Mar;12(1):75-95.
3 Martin PD, Warwick MJ, Dane AL, Hill SJ, Giles PB, Phillips PJ, Lenz E: Metabolism, excretion, and pharmacokinetics of rosuvastatin in healthy adult male volunteers. Clin Ther. 2003 Nov;25(11):2822-35.
4 BDDCS predictions, self-correcting aspects of BDDCS assignments, BDDCS assignment corrections, and classification for more than 175 additional drugs
5 Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
6 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.
7 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
8 An FDA phase I clinical trial of quinacrine sterilization (QS). Int J Gynaecol Obstet. 2003 Oct;83 Suppl 2:S45-9.
9 New dimension of statin action on ApoB atherogenicity. Clin Cardiol. 2003 Jan;26(1 Suppl 1):I7-10.
10 Drug and bile acid transporters in rosuvastatin hepatic uptake: function, expression, and pharmacogenetics. Gastroenterology. 2006 May;130(6):1793-806.
11 Involvement of multiple transporters in the hepatobiliary transport of rosuvastatin. Drug Metab Dispos. 2008 Oct;36(10):2014-23.
12 The contribution of organic anion transporters OAT1 and OAT3 to the renal uptake of rosuvastatin. J Pharmacol Exp Ther. 2007 Sep;322(3):1221-7.
13 Effects of acid and lactone forms of eight HMG-CoA reductase inhibitors on CYP-mediated metabolism and MDR1-mediated transport. Pharm Res. 2006 Mar;23(3):506-12.
14 Pharmacokinetics of rosuvastatin when coadministered with rifampicin in healthy males: a randomized, single-blind, placebo-controlled, crossover study. Clin Ther. 2008 Jul;30(7):1283-9.
15 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.
16 Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47.
17 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.
18 Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
19 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.
20 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.
21 Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
22 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.
23 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.
24 Progesterone and testosterone hydroxylation by cytochromes P450 2C19, 2C9, and 3A4 in human liver microsomes. Arch Biochem Biophys. 1997 Oct 1;346(1):161-9.
25 Tamoxifen inhibits cytochrome P450 2C9 activity in breast cancer patients. J Chemother. 2006 Aug;18(4):421-4.
26 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.
27 Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
28 Drug-drug interactions with imatinib: an observational study. Medicine (Baltimore). 2016 Oct;95(40):e5076.
29 Drug interactions with calcium channel blockers: possible involvement of metabolite-intermediate complexation with CYP3A. Drug Metab Dispos. 2000 Feb;28(2):125-30.
30 New insights into the structural features and functional relevance of human cytochrome P450 2C9. Part I. Curr Drug Metab. 2009 Dec;10(10):1075-126.
31 A potential role for the estrogen-metabolizing cytochrome P450 enzymes in human breast carcinogenesis. Breast Cancer Res Treat. 2003 Dec;82(3):191-7.
32 A mechanistic approach to antiepileptic drug interactions. Ann Pharmacother. 1998 May;32(5):554-63.
33 Catalytic properties of polymorphic human cytochrome P450 1B1 variants. Carcinogenesis. 1999 Aug;20(8):1607-13.
34 Cytochrome P450 isoforms catalyze formation of catechol estrogen quinones that react with DNA. Metabolism. 2007 Jul;56(7):887-94.
35 The influence of metabolic gene polymorphisms on urinary 1-hydroxypyrene concentrations in Chinese coke oven workers. Sci Total Environ. 2007 Aug 1;381(1-3):38-46.
36 A common CYP1B1 polymorphism is associated with 2-OHE1/16-OHE1 urinary estrone ratio. Clin Chem Lab Med. 2005;43(7):702-6.
37 Cytochromes P450 in crustacea. Comp Biochem Physiol C Pharmacol Toxicol Endocrinol. 1998 Nov;121(1-3):157-72.
38 Metabolism of retinoids and arachidonic acid by human and mouse cytochrome P450 1b1. Drug Metab Dispos. 2004 Aug;32(8):840-7.
39 Oxidation of xenobiotics by recombinant human cytochrome P450 1B1. Drug Metab Dispos. 1997 May;25(5):617-22.
40 Metabolism of melatonin by human cytochromes p450. Drug Metab Dispos. 2005 Apr;33(4):489-94.
41 Human CYP1B1 and anticancer agent metabolism: mechanism for tumor-specific drug inactivation? J Pharmacol Exp Ther. 2001 Feb;296(2):537-41.
42 Involvement of the drug transporters p glycoprotein and multidrug resistance-associated protein Mrp2 in telithromycin transport. Antimicrob Agents Chemother. 2006 Jan;50(1):80-7.
43 Dose-dependent disposition of methotrexate in Abcc2 and Abcc3 gene knockout murine models. Drug Metab Dispos. 2011 Nov;39(11):2155-61.
44 Mammalian multidrug-resistance proteins (MRPs). Essays Biochem. 2011 Sep 7;50(1):179-207.
45 Enhancing chemosensitivity in oral squamous cell carcinoma by lentivirus vector-mediated RNA interference targeting EGFR and MRP2. Oncol Lett. 2016 Sep;12(3):2107-2114.
46 Multidrug resistance associated protein 2 mediates transport of prostaglandin E2. Liver Int. 2006 Apr;26(3):362-8.
47 Lentivirus-mediated RNAi silencing targeting ABCC2 increasing the sensitivity of a human nasopharyngeal carcinoma cell line against cisplatin. J Transl Med. 2008 Oct 4;6:55.
48 Effect of acetaminophen on expression and activity of rat liver multidrug resistance-associated protein 2 and P-glycoprotein. Biochem Pharmacol. 2004 Aug 15;68(4):791-8.
49 Small intestinal efflux mediated by MRP2 and BCRP shifts sulfasalazine intestinal permeability from high to low, enabling its colonic targeting. Am J Physiol Gastrointest Liver Physiol. 2009 Aug;297(2):G371-7.
50 Delineating the contribution of secretory transporters in the efflux of etoposide using Madin-Darby canine kidney (MDCK) cells overexpressing P-glycoprotein (Pgp), multidrug resistance-associated protein (MRP1), and canalicular multispecific organic anion transporter (cMOAT). Drug Metab Dispos. 2002 Apr;30(4):457-63.
51 Multidrug Resistance-Associated Protein 2 (MRP2) Mediated Transport of Oxaliplatin-Derived Platinum in Membrane Vesicles. PLoS One. 2015 Jul 1;10(7):e0130727.
52 Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
53 MDR1 (ABCB1) G1199A (Ser400Asn) polymorphism alters transepithelial permeability and sensitivity to anticancer agents. Cancer Chemother Pharmacol. 2009 Jun;64(1):183-8.
54 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.
55 Folate transporter expression decreases in the human placenta throughout pregnancy and in pre-eclampsia. Pregnancy Hypertens. 2012 Apr;2(2):123-31.
56 Comparative studies on in vitro methods for evaluating in vivo function of MDR1 P-glycoprotein. Pharm Res. 2001 Dec;18(12):1660-8.
57 Antiestrogens and steroid hormones: substrates of the human P-glycoprotein. Biochem Pharmacol. 1994 Jul 19;48(2):287-92.
58 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.
59 Doxorubicin transport by RALBP1 and ABCG2 in lung and breast cancer. Int J Oncol. 2007 Mar;30(3):717-25.
60 Wild-type breast cancer resistance protein (BCRP/ABCG2) is a methotrexate polyglutamate transporter. Cancer Res. 2003 Sep 1;63(17):5538-43.
61 The effect of low pH on breast cancer resistance protein (ABCG2)-mediated transport of methotrexate, 7-hydroxymethotrexate, methotrexate diglutamate, folic acid, mitoxantrone, topotecan, and resveratrol in in vitro drug transport models. Mol Pharmacol. 2007 Jan;71(1):240-9.
62 Role of BCRP as a biomarker for predicting resistance to 5-fluorouracil in breast cancer. Cancer Chemother Pharmacol. 2009 May;63(6):1103-10.
63 Inhibiting the function of ABCB1 and ABCG2 by the EGFR tyrosine kinase inhibitor AG1478. Biochem Pharmacol. 2009 Mar 1;77(5):781-93.
64 Sterol transport by the human breast cancer resistance protein (ABCG2) expressed in Lactococcus lactis. J Biol Chem. 2003 Jun 6;278(23):20645-51.
65 The phytoestrogen genistein enhances multidrug resistance in breast cancer cell lines by translational regulation of ABC transporters. Cancer Lett. 2016 Jun 28;376(1):165-72.
66 Curcumin inhibits the activity of ABCG2/BCRP1, a multidrug resistance-linked ABC drug transporter in mice. Pharm Res. 2009 Feb;26(2):480-7.
67 Imatinib mesylate (STI571) is a substrate for the breast cancer resistance protein (BCRP)/ABCG2 drug pump. Blood. 2004 Nov 1;104(9):2940-2.
68 Preclinical Mouse Models To Study Human OATP1B1- and OATP1B3-Mediated Drug-Drug Interactions in Vivo. Mol Pharm. 2015 Dec 7;12(12):4259-69.
69 Organic anion transporting polypeptide 1B1: a genetically polymorphic transporter of major importance for hepatic drug uptake. Pharmacol Rev. 2011 Mar;63(1):157-81.
70 Contribution of OATP1B1 and OATP1B3 to the disposition of sorafenib and sorafenib-glucuronide. Clin Cancer Res. 2013 Mar 15;19(6):1458-66.
71 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.
72 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.
73 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.
74 Rifampicin alters atorvastatin plasma concentration on the basis of SLCO1B1 521T>C polymorphism. Clin Chim Acta. 2009 Jul;405(1-2):49-52.
75 FDA Drug Development and Drug Interactions
76 Differential effect of genetic variants of Na(+)-taurocholate co-transporting polypeptide (NTCP) and organic anion-transporting polypeptide 1B1 (OATP1B1) on the uptake of HMG-CoA reductase inhibitors. Xenobiotica. 2011 Jan;41(1):24-34.
77 Transporter-mediated influx and efflux mechanisms of pitavastatin, a new inhibitor of HMG-CoA reductase. J Pharm Pharmacol. 2005 Oct;57(10):1305-11.
78 Identification of thyroid hormone transporters. Biochem Biophys Res Commun. 1999 Jan 19;254(2):497-501.
79 Ethnicity-dependent polymorphism in Na+-taurocholate cotransporting polypeptide (SLC10A1) reveals a domain critical for bile acid substrate recognition. J Biol Chem. 2004 Feb 20;279(8):7213-22.
80 Modulation by drugs of human hepatic sodium-dependent bile acid transporter (sodium taurocholate cotransporting polypeptide) activity. J Pharmacol Exp Ther. 1999 Dec;291(3):1204-9.
81 Differential inhibition of rat and human Na+-dependent taurocholate cotransporting polypeptide (NTCP/SLC10A1)by bosentan: a mechanism for species differences in hepatotoxicity. J Pharmacol Exp Ther. 2007 Jun;321(3):1170-8.
82 Methotrexate-loxoprofen interaction: involvement of human organic anion transporters hOAT1 and hOAT3. Drug Metab Pharmacokinet. 2004 Oct;19(5):369-74.
83 Human organic anion transporters and human organic cation transporters mediate renal transport of prostaglandins. J Pharmacol Exp Ther. 2002 Apr;301(1):293-8.
84 Human organic anion transporters and human organic cation transporters mediate renal antiviral transport. J Pharmacol Exp Ther. 2002 Mar;300(3):918-24.
85 Identification and characterization of human organic anion transporter 3 expressing predominantly in the kidney. Mol Pharmacol. 2001 May;59(5):1277-86.
86 Prediction of the overall renal tubular secretion and hepatic clearance of anionic drugs and a renal drug-drug interaction involving organic anion transporter 3 in humans by in vitro uptake experiments. Drug Metab Dispos. 2011 Jun;39(6):1031-8.
87 Murine renal organic anion transporters mOAT1 and mOAT3 facilitate the transport of neuroactive tryptophan metabolites. Am J Physiol Cell Physiol. 2005 Nov;289(5):C1075-84.
88 Organic anion transporter 3 is involved in the brain-to-blood efflux transport of thiopurine nucleobase analogs. J Neurochem. 2004 Aug;90(4):931-41.
89 Aspirin and probenecid inhibit organic anion transporter 3-mediated renal uptake of cilostazol and probenecid induces metabolism of cilostazol in the rat. Drug Metab Dispos. 2014 Jun;42(6):996-1007.
90 Expression of organic anion transporter 2 in the human kidney and its potential role in the tubular secretion of guanine-containing antiviral drugs. Drug Metab Dispos. 2012 Mar;40(3):617-24.
91 Interaction of methotrexate with organic-anion transporting polypeptide 1A2 and its genetic variants. J Pharmacol Exp Ther. 2006 Aug;318(2):521-9.
92 Localization of organic anion transporting polypeptide 4 (Oatp4) in rat liver and comparison of its substrate specificity with Oatp1, Oatp2 and Oatp3. Pflugers Arch. 2001 Nov;443(2):188-95.
93 Environmental and genetic factors affecting transport of imatinib by OATP1A2. Clin Pharmacol Ther. 2011 Jun;89(6):816-20.
94 Influence of the flavonoids apigenin, kaempferol, and quercetin on the function of organic anion transporting polypeptides 1A2 and 2B1. Biochem Pharmacol. 2010 Dec 1;80(11):1746-53.
95 Human organic anion-transporting polypeptide OATP-A (SLC21A3) acts in concert with P-glycoprotein and multidrug resistance protein 2 in the vectorial transport of Saquinavir in Hep G2 cells. Mol Pharm. 2004 Jan 12;1(1):49-56.
96 Uptake of enalapril and expression of organic anion transporting polypeptide 1 in zonal, isolated rat hepatocytes. Drug Metab Dispos. 2000 Jul;28(7):801-6.
97 Molecular and functional characterization of an organic anion transporting polypeptide cloned from human liver. Gastroenterology. 1995 Oct;109(4):1274-82.
98 Identification of thyroid hormone transporters in humans: different molecules are involved in a tissue-specific manner. Endocrinology. 2001 May;142(5):2005-12.
99 Involvement of influx and efflux transport systems in gastrointestinal absorption of celiprolol. J Pharm Sci. 2009 Jul;98(7):2529-39.
100 LST-2, a human liver-specific organic anion transporter, determines methotrexate sensitivity in gastrointestinal cancers. Gastroenterology. 2001 Jun;120(7):1689-99.
101 Effect of pregnane X receptor ligands on transport mediated by human OATP1B1 and OATP1B3. Eur J Pharmacol. 2008 Apr 14;584(1):57-65.
102 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.
103 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.
104 Impact of OATP transporters on pharmacokinetics. Br J Pharmacol. 2009 Oct;158(3):693-705.
105 Molecular identification and characterization of novel members of the human organic anion transporter (OATP) family. Biochem Biophys Res Commun. 2000 Jun 24;273(1):251-60.
106 The Transporter Classification Database (TCDB): recent advances. Nucleic Acids Res. 2016 Jan 4;44(D1):D372-9. (ID: 2.A.60.1.20)
107 Small-Dosing Clinical Study: Pharmacokinetic, Pharmacogenomic (SLCO2B1 and ABCG2), and Interaction (Atorvastatin and Grapefruit Juice) Profiles of 5 Probes for OATP2B1 and BCRP. J Pharm Sci. 2017 Sep;106(9):2688-2694.
108 Functional characterization of pH-sensitive organic anion transporting polypeptide OATP-B in human. J Pharmacol Exp Ther. 2004 Feb;308(2):438-45.
109 Human platelets express organic anion-transporting peptide 2B1, an uptake transporter for atorvastatin. Drug Metab Dispos. 2009 May;37(5):1129-37.
110 pH-sensitive interaction of HMG-CoA reductase inhibitors (statins) with organic anion transporting polypeptide 2B1. Mol Pharm. 2011 Aug 1;8(4):1303-13.
111 Drug-drug interaction between pitavastatin and various drugs via OATP1B1. Drug Metab Dispos. 2006 Jul;34(7):1229-36.
112 Drug Interactions in Infectious Diseases.
113 Substrate-dependent drug-drug interactions between gemfibrozil, fluvastatin and other organic anion-transporting peptide (OATP) substrates on OATP1B1, OATP2B1, and OATP1B3. Drug Metab Dispos. 2007 Aug;35(8):1308-14.
114 A randomized, double-blind trial comparing the efficacy and safety of pitavastatin versus pravastatin in patients with primary hypercholesterolemia. Atherosclerosis. 2002 Jun;162(2):373-9.
115 Equally potent inhibitors of cholesterol synthesis in human hepatocytes have distinguishable effects on different cytochrome P450 enzymes. Biopharm Drug Dispos. 2000 Dec;21(9):353-64.
116 Emerging therapies for multiple myeloma. Expert Opin Emerg Drugs. 2009 Mar;14(1):99-127.
117 Cholesterol-lowering effect of NK-104, a 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor, in guinea pig model of hyperlipidemia. Arzneimittelforschung. 2001;51(3):197-203.
118 Emerging drugs in peripheral arterial disease. Expert Opin Emerg Drugs. 2006 Mar;11(1):75-90.
119 Microarray and biochemical analysis of lovastatin-induced apoptosis of squamous cell carcinomas. Neoplasia. 2002 Jul-Aug;4(4):337-46.
120 Inhibitory effect of delta-tocotrienol, a HMG CoA reductase inhibitor, on monocyte-endothelial cell adhesion. J Nutr Sci Vitaminol (Tokyo). 2002 Oct;48(5):332-7.
121 Product Information. Nexletol (bempedoic acid). Esperion Therapeutics, Ann Arbor, MI.
122 Product Information. Crestor (rosuvastatin). AstraZeneca Pharma Inc, Mississauga, ON.
123 Product Information. Kynamro (mipomersen). Genzyme Corporation, Cambridge, MA.
124 Cerner Multum, Inc. "Australian Product Information.".
125 Product Information. Juxtapid (lomitapide). Aegerion Pharmaceuticals Inc, Cambridge, MA.
126 Cerner Multum, Inc. "UK Summary of Product Characteristics.".
127 Product Information. Piqray (alpelisib). Novartis Pharmaceuticals, East Hanover, NJ.
128 Product Information. Prevymis (letermovir). Merck & Company Inc, Whitehouse Station, NJ.
129 Product Information. Olysio (simeprevir). Janssen Pharmaceuticals, Titusville, NJ.
130 Product Information. Epclusa (sofosbuvir-velpatasvir). Gilead Sciences, Foster City, CA.
131 Product Information. Accolate (zafirlukast). Zeneca Pharmaceuticals, Wilmington, DE.
132 Product Information. Rukobia (fostemsavir). ViiV Healthcare, Research Triangle Park, NC.
133 Neuvonen PJ, Niemi M, Backman JT "Drug interactions with lipid-lowering drugs: Mechanisms and clinical relevance." Clin Pharmacol Ther 80 (2006): 565-81. [PMID: 17178259]
134 Product Information. Tabrecta (capmatinib). Novartis Pharmaceuticals, East Hanover, NJ.
135 Product Information. Zydelig (idelalisib). Gilead Sciences, Foster City, CA.
136 Product Information. Reyvow (lasmiditan). Lilly, Eli and Company, Indianapolis, IN.
137 Product Information. Varubi (rolapitant). Tesaro Inc., Waltham, MA.