General Information of Drug (ID: DM6A0X7)

Drug Name
Pravastatin
Synonyms
Eptastatin; Oliprevin; Pravastatina; Pravastatine; Pravastatinum; Pravator; Vasten; Pravastatin Sodium Salt; Pravastatina [Spanish]; Pravastatine [French]; Pravastatinum [Latin]; KS-5015; Pravachol (TN); Pravastatin (INN); Pravastatin [INN:BAN]; Pravastatin tert-Octylamine Salt; Pravator (TN); RMS-431; Selektine (TN); SQ-31,000; (3R,5R)-3,5-dihydroxy-7-[(1S,2S,6S,8S,8aR)-6-hydroxy-2-methyl-8-{[(2S)-2-methylbutanoyl]oxy}-1,2,6,7,8,8a-hexahydronaphthalen-1-yl]heptanoic acid; (3R,5R)-7-[(1S,2S,6S,8S,8aR)-6-hydroxy-2-methyl-8-[(2S)-2-methylbutanoyl]oxy-1,2,6,7,8,8a-hexahydronaphthalen-1-yl]-3,5-dihydroxyheptanoic acid; 1,2,6,7,8,8a-hexahydro-beta,delta,6-trihydroxy-2-methyl-8-(2-methyl-1-oxobutoxy)-, (1S-(1alpha(betaS*,deltaS*),2alpha,6alpha,8beta(R*),8aalpha))-1-Naphthaleneheptanoic acid
Indication
Disease Entry ICD 11 Status REF
Hypercholesterolaemia 5C80.0 Approved [1], [2]
Therapeutic Class
Anticholesteremic Agents
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 1 Molecular Weight (mw) 424.5
Topological Polar Surface Area (xlogp) 1.6
Rotatable Bond Count (rotbonds) 11
Hydrogen Bond Donor Count (hbonddonor) 4
Hydrogen Bond Acceptor Count (hbondacc) 7
ADMET Property
Absorption AUC
The area under the plot of plasma concentration (AUC) of drug is 60-90 mcgh/L [3]
Absorption Cmax
The maximum plasma concentration (Cmax) of drug is 30-55 mcg/L [3]
BDDCS Class
Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 3: high solubility and low permeability [4]
Bioavailability
The bioavailability of drug is 17% [3]
Clearance
4-11 L/min for children [5]
Elimination
From the administered dose of pravastatin, about 70% is eliminated in the feces while about 20% is obtained in the urine [6]
Half-life
The concentration or amount of drug in body reduced by one-half in 1.8 hours [3]
Metabolism
The drug is metabolized via the liver [3]
MRTD
The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 1.57112 micromolar/kg/day [7]
Unbound Fraction
The unbound fraction of drug in plasma is 0.5% [8]
Vd
The volume of distribution (Vd) of drug is 0.5 L/kg [5]
Water Solubility
The ability of drug to dissolve in water is measured as 300 mg/mL [4]
Chemical Identifiers
Formula
C23H36O7
IUPAC Name
(3R,5R)-7-[(1S,2S,6S,8S,8aR)-6-hydroxy-2-methyl-8-[(2S)-2-methylbutanoyl]oxy-1,2,6,7,8,8a-hexahydronaphthalen-1-yl]-3,5-dihydroxyheptanoic acid
Canonical SMILES
CC[C@H](C)C(=O)O[C@H]1C[C@@H](C=C2[C@H]1[C@H]([C@H](C=C2)C)CC[C@H](C[C@H](CC(=O)O)O)O)O
InChI
InChI=1S/C23H36O7/c1-4-13(2)23(29)30-20-11-17(25)9-15-6-5-14(3)19(22(15)20)8-7-16(24)10-18(26)12-21(27)28/h5-6,9,13-14,16-20,22,24-26H,4,7-8,10-12H2,1-3H3,(H,27,28)/t13-,14-,16+,17+,18+,19-,20-,22-/m0/s1
InChIKey
TUZYXOIXSAXUGO-PZAWKZKUSA-N
Cross-matching ID
PubChem CID
54687
ChEBI ID
CHEBI:63618
CAS Number
81093-37-0
DrugBank ID
DB00175
TTD ID
D02RQU
VARIDT ID
DR00045
INTEDE ID
DR1327
ACDINA ID
D00548

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
Probable small intestine urate exporter (SLC17A4) DTHE530 S17A4_HUMAN Substrate [10]
Organic anion transporter 7 (SLC22A9) DTDI5S3 S22A9_HUMAN Substrate [11]
Bile salt export pump (ABCB11) DTJ0EW4 ABCBB_HUMAN Substrate [12]
Multidrug resistance-associated protein 2 (ABCC2) DTFI42L MRP2_HUMAN Substrate [13]
Organic anion transporter 4 (SLC22A11) DT06JWZ S22AB_HUMAN Substrate [14]
Organic anion transporting polypeptide 2B1 (SLCO2B1) DTPFTEQ SO2B1_HUMAN Substrate [15]
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [16]
Organic anion transporting polypeptide 1B1 (SLCO1B1) DT3D8F0 SO1B1_HUMAN Substrate [17]
Organic anion transporting polypeptide 1B3 (SLCO1B3) DT9C1TS SO1B3_HUMAN Substrate [18]
Organic anion transporter 3 (SLC22A8) DTVP67E S22A8_HUMAN Substrate [19]
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [20]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Substrate [21]
Cytochrome P450 2C9 (CYP2C9) DE5IED8 CP2C9_HUMAN Substrate [22]
Cytochrome P450 3A5 (CYP3A5) DEIBDNY CP3A5_HUMAN Substrate [23]
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
Bile salt export pump (ABCB11) DTP BSEP 2.41E-01 -3.08E-02 -2.35E-01
Breast cancer resistance protein (ABCG2) DTP BCRP 2.28E-08 -3.66E-01 -8.07E-01
Probable small intestine urate exporter (SLC17A4) DTP SLC17A4 1.00E-02 -1.74E-01 -8.13E-01
Multidrug resistance-associated protein 2 (ABCC2) DTP MRP2 4.30E-02 -2.29E-01 -9.10E-01
Organic anion transporter 7 (SLC22A9) DTP OAT7 1.92E-04 -4.34E-01 -1.40E+00
Organic anion transporting polypeptide 1B3 (SLCO1B3) DTP OATP1B3 1.65E-01 -6.07E-02 -3.77E-01
Organic anion transporting polypeptide 1B1 (SLCO1B1) DTP OATP1B1 3.27E-01 -5.78E-02 -3.84E-01
Organic anion transporter 4 (SLC22A11) DTP OAT4 3.76E-03 -3.49E-01 -8.70E-01
Cytochrome P450 3A5 (CYP3A5) DME CYP3A5 3.65E-02 -8.90E-02 -5.58E-01
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 Pravastatin
DDI Drug Name DDI Drug ID Severity Mechanism Disease REF
Mipomersen DMGSRN1 Major Increased risk of hepatotoxicity by the combination of Pravastatin and Mipomersen. Hyper-lipoproteinaemia [5C80] [123]
Teriflunomide DMQ2FKJ Major Increased risk of hepatotoxicity by the combination of Pravastatin and Teriflunomide. Hyper-lipoproteinaemia [5C80] [124]
BMS-201038 DMQTAGO Major Increased risk of hepatotoxicity by the combination of Pravastatin and BMS-201038. Hyper-lipoproteinaemia [5C80] [125]
Coadministration of a Drug Treating the Disease Different from Pravastatin (Comorbidity)
DDI Drug Name DDI Drug ID Severity Mechanism Comorbidity REF
Remdesivir DMBFZ6L Moderate Increased risk of hepatotoxicity by the combination of Pravastatin and Remdesivir. 1D6YCoronavirus Disease 2019 [1D6YCoronavirus Disease 2019] [126]
Thioguanine DM7NKEV Moderate Increased risk of hepatotoxicity by the combination of Pravastatin and Thioguanine. Acute myeloid leukaemia [2A60] [127]
Midostaurin DMI6E0R Moderate Decreased clearance of Pravastatin due to the transporter inhibition by Midostaurin. Acute myeloid leukaemia [2A60] [128]
Arn-509 DMT81LZ Moderate Accelerated clearance of Pravastatin due to the transporter induction by Arn-509. Acute myeloid leukaemia [2A60] [128]
Bedaquiline DM3906J Moderate Increased risk of hepatotoxicity by the combination of Pravastatin and Bedaquiline. Antimicrobial drug resistance [MG50-MG52] [129]
Erythromycin DM4K7GQ Moderate Decreased clearance of Pravastatin due to the transporter inhibition by Erythromycin. Bacterial infection [1A00-1C4Z] [130]
Clarithromycin DM4M1SG Moderate Decreased clearance of Pravastatin due to the transporter inhibition by Clarithromycin. Bacterial infection [1A00-1C4Z] [130]
Ag-221 DMS0ZBI Moderate Decreased clearance of Pravastatin due to the transporter inhibition by Ag-221. BCR-ABL1-negative chronic myeloid leukaemia [2A41] [126]
Pexidartinib DMS2J0Z Major Increased risk of hepatotoxicity by the combination of Pravastatin and Pexidartinib. Bone/articular cartilage neoplasm [2F7B] [131]
Anisindione DM2C48U Minor Increased risk of bleeding by the combination of Pravastatin and Anisindione. Coagulation defect [3B10] [132]
MK-8228 DMOB58Q Moderate Decreased clearance of Pravastatin due to the transporter inhibition by MK-8228. Cytomegaloviral disease [1D82] [133]
Cannabidiol DM0659E Moderate Increased risk of hepatotoxicity by the combination of Pravastatin and Cannabidiol. Epileptic encephalopathy [8A62] [128]
ABT-450 DMFW860 Major Decreased clearance of Pravastatin due to the transporter inhibition by ABT-450. Hepatitis virus infection [1E50-1E51] [134]
Simeprevir DMLUA9D Moderate Decreased clearance of Pravastatin due to the transporter inhibition by Simeprevir. Hepatitis virus infection [1E50-1E51] [135]
GS-9857 DMYU6P5 Major Decreased clearance of Pravastatin due to the transporter inhibition by GS-9857. Hepatitis virus infection [1E50-1E51] [136]
Brentuximab vedotin DMWLC57 Moderate Increased risk of peripheral neuropathy by the combination of Pravastatin and Brentuximab vedotin. Hodgkin lymphoma [2B30] [137]
Fostemsavir DM50ILT Moderate Decreased clearance of Pravastatin due to the transporter inhibition by Fostemsavir. Human immunodeficiency virus disease [1C60-1C62] [138]
Nevirapine DM6HX9B Moderate Increased metabolism of Pravastatin caused by Nevirapine mediated induction of CYP450 enzyme. Human immunodeficiency virus disease [1C60-1C62] [139]
Cobicistat DM6L4H2 Moderate Decreased clearance of Pravastatin due to the transporter inhibition by Cobicistat. Human immunodeficiency virus disease [1C60-1C62] [126]
Efavirenz DMC0GSJ Moderate Increased metabolism of Pravastatin caused by Efavirenz mediated induction of CYP450 enzyme. Human immunodeficiency virus disease [1C60-1C62] [139]
Zalcitabine DMH7MUV Moderate Increased risk of peripheral neuropathy by the combination of Pravastatin and Zalcitabine. Human immunodeficiency virus disease [1C60-1C62] [140]
Ritonavir DMU764S Moderate Increased metabolism of Pravastatin caused by Ritonavir mediated induction of UGT. Human immunodeficiency virus disease [1C60-1C62] [134]
Methotrexate DM2TEOL Moderate Increased risk of hepatotoxicity by the combination of Pravastatin and Methotrexate. Leukaemia [2A60-2B33] [128]
Porfimer Sodium DM7ZWNY Moderate Increased risk of photosensitivity reactions by the combination of Pravastatin and Porfimer Sodium. Lung cancer [2C25] [141]
Calaspargase pegol DMQZBXI Moderate Increased risk of hepatotoxicity by the combination of Pravastatin and Calaspargase pegol. Malignant haematopoietic neoplasm [2B33] [142]
Idelalisib DM602WT Moderate Increased risk of hepatotoxicity by the combination of Pravastatin and Idelalisib. Mature B-cell leukaemia [2A82] [143]
Clofarabine DMCVJ86 Moderate Increased risk of hepatotoxicity by the combination of Pravastatin and Clofarabine. Mature B-cell lymphoma [2A85] [144]
Dabrafenib DMX6OE3 Moderate Decreased clearance of Pravastatin due to the transporter inhibition by Dabrafenib. Melanoma [2C30] [126]
Thalidomide DM70BU5 Moderate Increased risk of peripheral neuropathy by the combination of Pravastatin and Thalidomide. Multiple myeloma [2A83] [140]
Bortezomib DMNO38U Moderate Increased risk of peripheral neuropathy by the combination of Pravastatin and Bortezomib. Multiple myeloma [2A83] [140]
Darolutamide DMV7YFT Moderate Decreased clearance of Pravastatin due to the transporter inhibition by Darolutamide. Prostate cancer [2C82] [128]
Leflunomide DMR8ONJ Major Increased risk of hepatotoxicity by the combination of Pravastatin and Leflunomide. Rheumatoid arthritis [FA20] [124]
Epirubicin DMPDW6T Moderate Increased risk of hepatotoxicity by the combination of Pravastatin and Epirubicin. Solid tumour/cancer [2A00-2F9Z] [126]
Naltrexone DMUL45H Moderate Increased risk of hepatotoxicity by the combination of Pravastatin and Naltrexone. Substance abuse [6C40] [145]
Warfarin DMJYCVW Minor Increased risk of bleeding by the combination of Pravastatin and Warfarin. Supraventricular tachyarrhythmia [BC81] [132]
Dicumarol DMFQCB1 Minor Increased risk of bleeding by the combination of Pravastatin and Dicumarol. Thrombosis [DB61-GB90] [132]
⏷ Show the Full List of 36 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
FD&C blue no. 1 E00263 19700 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 lauryl sulfate E00464 3423265 Emulsifying agent; Modified-release agent; Penetration agent; Solubilizing agent; Surfactant; lubricant
Sodium stearyl fumarate E00545 23665634 lubricant
Aluminum trihydroxide E00505 10176082 Alkalizing agent; Vaccine adjuvant
Beta-D-lactose E00099 6134 Diluent; Dry powder inhaler carrier; Lyophilization aid
Calcium hydrogenphosphate E00294 24441 Diluent
Calcium stearate E00244 15324 lubricant
Carbonic acid disodium salt E00199 10340 Alkalizing agent; Buffering agent; Diluent; Dispersing agent
Carmellose sodium E00625 Not Available Disintegrant
Crospovidone E00626 Not Available Disintegrant
Dihydroxyaluminum sodium carbonate E00573 23697815 Diluent
Disodium hydrogenorthophosphate E00283 24203 Buffering agent; Complexing agent
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 aluminum silicate E00462 3084116 Adsorbent; Binding agent; Disintegrant; Suspending agent; Viscosity-controlling agent
Magnesium oxide E00232 14792 Anticaking agent; Diluent; Emulsifying agent; Glidant; Tonicity agent
Magnesium stearate E00208 11177 lubricant
Polyethylene glycol 6000 E00655 Not Available Coating agent; Diluent; Ointment base; Plasticizing agent; Solvent; Suppository base; lubricant
Polyoxyl 35 castor oil E00660 Not Available Emulsifying agent; Solubilizing agent; Surfactant
Povidone E00667 Not Available Binding agent; Coating agent; Disintegrant; Film/membrane-forming agent; Solubilizing agent; Suspending agent
Silicon dioxide E00670 Not Available Anticaking agent; Opacifying agent; Viscosity-controlling agent
Sodium bicarbonate E00424 516892 Alkalizing agent; Diluent
Talc E00520 16211421 Anticaking agent; Diluent; Glidant; lubricant
Titanium dioxide E00322 26042 Coating agent; Colorant; Opacifying agent
Vinylpyrrolidone E00668 Not Available Binding agent; Coating agent; Disintegrant; Film/membrane-forming agent; Solubilizing agent; Suspending agent
Hydrophobic colloidal silica E00285 24261 Anticaking agent; Emulsion stabilizing agent; Glidant; Suspending agent; Viscosity-controlling agent
Cellulose microcrystalline E00698 Not Available Adsorbent; Suspending agent; Diluent
Pregelatinized starch E00674 Not Available Binding agent; Diluent; Disintegrant
⏷ Show the Full List of 33 Pharmaceutical Excipients of This Drug
Pharmaceutical Formulation
Formulation Name Drug Dosage Dosage Form Route
Pravastatin 40 mg tablet 40 mg Oral Tablet Oral
Pravastatin 10 mg tablet 10 mg Oral Tablet Oral
Pravastatin 20 mg tablet 20 mg Oral Tablet Oral
Pravastatin Sodium 40mg tablet 40mg Tablet Oral
Pravastatin Sodium 10mg tablet 10mg Tablet Oral
Pravastatin 80 mg tablet 80 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: 2953).
2 Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77.
3 Evidence-based review of statin use in patients with HIV on antiretroviral therapy. J Clin Transl Endocrinol. 2017 Feb 22;8:6-14. doi: 10.1016/j.jcte.2017.01.004. eCollection 2017 Jun.
4 BDDCS predictions, self-correcting aspects of BDDCS assignments, BDDCS assignment corrections, and classification for more than 175 additional drugs
5 Singhvi SM, Pan HY, Morrison RA, Willard DA: Disposition of pravastatin sodium, a tissue-selective HMG-CoA reductase inhibitor, in healthy subjects. Br J Clin Pharmacol. 1990 Feb;29(2):239-43.
6 An FDA phase I clinical trial of quinacrine sterilization (QS). Int J Gynaecol Obstet. 2003 Oct;83 Suppl 2:S45-9.
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 Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
9 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.
10 A Na+-phosphate cotransporter homologue (SLC17A4 protein) is an intestinal organic anion exporter. Am J Physiol Cell Physiol. 2012 Jun 1;302(11):C1652-60.
11 Variability in hepatic expression of organic anion transporter 7/SLC22A9, a novel pravastatin uptake transporter: impact of genetic and regulatory factors. Pharmacogenomics J. 2016 Aug;16(4):341-51.
12 Bile salt export pump (BSEP/ABCB11) can transport a nonbile acid substrate, pravastatin. J Pharmacol Exp Ther. 2005 Aug;314(2):876-82.
13 Role of transporters in the tissue-selective distribution and elimination of drugs: transporters in the liver, small intestine, brain and kidney. J Control Release. 2002 Jan 17;78(1-3):43-54.
14 Inhibition of human organic anion transporter 3 mediated pravastatin transport by gemfibrozil and the metabolites in humans. Xenobiotica. 2007 Apr;37(4):416-26.
15 Functional characterization of pH-sensitive organic anion transporting polypeptide OATP-B in human. J Pharmacol Exp Ther. 2004 Feb;308(2):438-45.
16 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.
17 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.
18 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.
19 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.
20 Tarascon Pocket Pharmacopoeia 2018 Classic Shirt-Pocket Edition.
21 Clinical pharmacokinetics of pravastatin: mechanisms of pharmacokinetic events. Clin Pharmacokinet. 2000 Dec;39(6):397-412.
22 In vitro comparative inhibition profiles of major human drug metabolising cytochrome P450 isozymes (CYP2C9, CYP2D6 and CYP3A4) by HMG-CoA reductase inhibitors. Eur J Clin Pharmacol. 1996;50(3):209-15.
23 Comparison of cytochrome P-450-dependent metabolism and drug interactions of the 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors lovastatin and pravastatin in the liver. Drug Metab Dispos. 1999 Feb;27(2):173-9.
24 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.
25 Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47.
26 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.
27 Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
28 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.
29 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.
30 Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
31 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.
32 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.
33 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.
34 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.
35 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.
36 Drug Interactions Flockhart Table
37 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.
38 Urinary 6 beta-hydroxycortisol excretion in rheumatoid arthritis. Br J Rheumatol. 1997 Jan;36(1):54-8.
39 Clinical pharmacokinetics of imatinib. Clin Pharmacokinet. 2005;44(9):879-94.
40 Kinetics and regulation of cytochrome P450-mediated etoposide metabolism. Drug Metab Dispos. 2004 Sep;32(9):993-1000.
41 Differential mechanism-based inhibition of CYP3A4 and CYP3A5 by verapamil. Drug Metab Dispos. 2005 May;33(5):664-71.
42 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.
43 Tamoxifen inhibits cytochrome P450 2C9 activity in breast cancer patients. J Chemother. 2006 Aug;18(4):421-4.
44 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.
45 Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
46 Drug-drug interactions with imatinib: an observational study. Medicine (Baltimore). 2016 Oct;95(40):e5076.
47 Drug interactions with calcium channel blockers: possible involvement of metabolite-intermediate complexation with CYP3A. Drug Metab Dispos. 2000 Feb;28(2):125-30.
48 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.
49 A potential role for the estrogen-metabolizing cytochrome P450 enzymes in human breast carcinogenesis. Breast Cancer Res Treat. 2003 Dec;82(3):191-7.
50 A mechanistic approach to antiepileptic drug interactions. Ann Pharmacother. 1998 May;32(5):554-63.
51 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.
52 Dose-dependent disposition of methotrexate in Abcc2 and Abcc3 gene knockout murine models. Drug Metab Dispos. 2011 Nov;39(11):2155-61.
53 Mammalian multidrug-resistance proteins (MRPs). Essays Biochem. 2011 Sep 7;50(1):179-207.
54 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.
55 Multidrug resistance associated protein 2 mediates transport of prostaglandin E2. Liver Int. 2006 Apr;26(3):362-8.
56 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.
57 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.
58 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.
59 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.
60 Multidrug Resistance-Associated Protein 2 (MRP2) Mediated Transport of Oxaliplatin-Derived Platinum in Membrane Vesicles. PLoS One. 2015 Jul 1;10(7):e0130727.
61 Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
62 MDR1 (ABCB1) G1199A (Ser400Asn) polymorphism alters transepithelial permeability and sensitivity to anticancer agents. Cancer Chemother Pharmacol. 2009 Jun;64(1):183-8.
63 Folate transporter expression decreases in the human placenta throughout pregnancy and in pre-eclampsia. Pregnancy Hypertens. 2012 Apr;2(2):123-31.
64 Comparative studies on in vitro methods for evaluating in vivo function of MDR1 P-glycoprotein. Pharm Res. 2001 Dec;18(12):1660-8.
65 Antiestrogens and steroid hormones: substrates of the human P-glycoprotein. Biochem Pharmacol. 1994 Jul 19;48(2):287-92.
66 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.
67 Doxorubicin transport by RALBP1 and ABCG2 in lung and breast cancer. Int J Oncol. 2007 Mar;30(3):717-25.
68 Wild-type breast cancer resistance protein (BCRP/ABCG2) is a methotrexate polyglutamate transporter. Cancer Res. 2003 Sep 1;63(17):5538-43.
69 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.
70 Role of BCRP as a biomarker for predicting resistance to 5-fluorouracil in breast cancer. Cancer Chemother Pharmacol. 2009 May;63(6):1103-10.
71 Inhibiting the function of ABCB1 and ABCG2 by the EGFR tyrosine kinase inhibitor AG1478. Biochem Pharmacol. 2009 Mar 1;77(5):781-93.
72 Sterol transport by the human breast cancer resistance protein (ABCG2) expressed in Lactococcus lactis. J Biol Chem. 2003 Jun 6;278(23):20645-51.
73 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.
74 Curcumin inhibits the activity of ABCG2/BCRP1, a multidrug resistance-linked ABC drug transporter in mice. Pharm Res. 2009 Feb;26(2):480-7.
75 Imatinib mesylate (STI571) is a substrate for the breast cancer resistance protein (BCRP)/ABCG2 drug pump. Blood. 2004 Nov 1;104(9):2940-2.
76 Preclinical Mouse Models To Study Human OATP1B1- and OATP1B3-Mediated Drug-Drug Interactions in Vivo. Mol Pharm. 2015 Dec 7;12(12):4259-69.
77 Organic anion transporting polypeptide 1B1: a genetically polymorphic transporter of major importance for hepatic drug uptake. Pharmacol Rev. 2011 Mar;63(1):157-81.
78 Contribution of OATP1B1 and OATP1B3 to the disposition of sorafenib and sorafenib-glucuronide. Clin Cancer Res. 2013 Mar 15;19(6):1458-66.
79 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.
80 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.
81 Rifampicin alters atorvastatin plasma concentration on the basis of SLCO1B1 521T>C polymorphism. Clin Chim Acta. 2009 Jul;405(1-2):49-52.
82 FDA Drug Development and Drug Interactions
83 Involvement of multiple transporters in the hepatobiliary transport of rosuvastatin. Drug Metab Dispos. 2008 Oct;36(10):2014-23.
84 Early identification of clinically relevant drug interactions with the human bile salt export pump (BSEP/ABCB11). Toxicol Sci. 2013 Dec;136(2):328-43.
85 Inhibition of transport across the hepatocyte canalicular membrane by the antibiotic fusidate. Biochem Pharmacol. 2002 Jul 1;64(1):151-8.
86 Methotrexate-loxoprofen interaction: involvement of human organic anion transporters hOAT1 and hOAT3. Drug Metab Pharmacokinet. 2004 Oct;19(5):369-74.
87 Human organic anion transporters and human organic cation transporters mediate renal transport of prostaglandins. J Pharmacol Exp Ther. 2002 Apr;301(1):293-8.
88 Human organic anion transporters and human organic cation transporters mediate renal antiviral transport. J Pharmacol Exp Ther. 2002 Mar;300(3):918-24.
89 Identification and characterization of human organic anion transporter 3 expressing predominantly in the kidney. Mol Pharmacol. 2001 May;59(5):1277-86.
90 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.
91 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.
92 Transporter-mediated influx and efflux mechanisms of pitavastatin, a new inhibitor of HMG-CoA reductase. J Pharm Pharmacol. 2005 Oct;57(10):1305-11.
93 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.
94 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.
95 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.
96 Characterization of methotrexate transport and its drug interactions with human organic anion transporters. J Pharmacol Exp Ther. 2002 Aug;302(2):666-71.
97 The role of the intracellular glutamate gradient in driving organic anion transporter function.
98 Human organic anion transporters mediate the transport of tetracycline. Jpn J Pharmacol. 2002 Jan;88(1):69-76.
99 Interactions of human organic anion transporters with diuretics. J Pharmacol Exp Ther. 2004 Mar;308(3):1021-9.
100 Inhibitory effects of angiotensin II receptor antagonists and leukotriene receptor antagonists on the transport of human organic anion transporter 4. J Pharm Pharmacol. 2006 Nov;58(11):1499-505.
101 Cellular Uptake of Levocetirizine by Organic Anion Transporter 4. J Pharm Sci. 2017 Sep;106(9):2895-2898.
102 Involvement of uric acid transporters in alteration of serum uric acid level by angiotensin II receptor blockers. Pharm Res. 2008 Mar;25(3):639-46.
103 LST-2, a human liver-specific organic anion transporter, determines methotrexate sensitivity in gastrointestinal cancers. Gastroenterology. 2001 Jun;120(7):1689-99.
104 Effect of pregnane X receptor ligands on transport mediated by human OATP1B1 and OATP1B3. Eur J Pharmacol. 2008 Apr 14;584(1):57-65.
105 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.
106 Impact of OATP transporters on pharmacokinetics. Br J Pharmacol. 2009 Oct;158(3):693-705.
107 Contribution of OATP2 (OATP1B1) and OATP8 (OATP1B3) to the hepatic uptake of pitavastatin in humans. J Pharmacol Exp Ther. 2004 Oct;311(1):139-46.
108 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.
109 The Transporter Classification Database (TCDB): recent advances. Nucleic Acids Res. 2016 Jan 4;44(D1):D372-9. (ID: 2.A.60.1.20)
110 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.
111 Human platelets express organic anion-transporting peptide 2B1, an uptake transporter for atorvastatin. Drug Metab Dispos. 2009 May;37(5):1129-37.
112 pH-sensitive interaction of HMG-CoA reductase inhibitors (statins) with organic anion transporting polypeptide 2B1. Mol Pharm. 2011 Aug 1;8(4):1303-13.
113 Drug-drug interaction between pitavastatin and various drugs via OATP1B1. Drug Metab Dispos. 2006 Jul;34(7):1229-36.
114 Drug Interactions in Infectious Diseases.
115 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.
116 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.
117 Emerging therapies for multiple myeloma. Expert Opin Emerg Drugs. 2009 Mar;14(1):99-127.
118 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.
119 New dimension of statin action on ApoB atherogenicity. Clin Cardiol. 2003 Jan;26(1 Suppl 1):I7-10.
120 Emerging drugs in peripheral arterial disease. Expert Opin Emerg Drugs. 2006 Mar;11(1):75-90.
121 Microarray and biochemical analysis of lovastatin-induced apoptosis of squamous cell carcinomas. Neoplasia. 2002 Jul-Aug;4(4):337-46.
122 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.
123 Product Information. Kynamro (mipomersen). Genzyme Corporation, Cambridge, MA.
124 Canadian Pharmacists Association.
125 Product Information. Juxtapid (lomitapide). Aegerion Pharmaceuticals Inc, Cambridge, MA.
126 Cerner Multum, Inc. "Australian Product Information.".
127 Product Information. Aubagio (teriflunomide). Genzyme Corporation, Cambridge, MA.
128 Cerner Multum, Inc. "UK Summary of Product Characteristics.".
129 Product Information. Sirturo (bedaquiline). Janssen Pharmaceuticals, Titusville, NJ.
130 Jacobson TA "Comparative pharmacokinetic interaction profiles of pravastatin, simvastatin, and atorvastatin when coadministered with cytochrome P450 inhibitors." Am J Cardiol 94 (2004): 1140-6. [PMID: 15518608]
131 Product Information. Turalio (pexidartinib). Daiichi Sankyo, Inc., Parsippany, NJ.
132 Jungnickel PW, Cantral KA, Maloley PA "Pravastatin: a new drug for the treatment of hypercholesterolemia." Clin Pharm 11 (1992): 677-89. [PMID: 1511541]
133 Product Information. Prevymis (letermovir). Merck & Company Inc, Whitehouse Station, NJ.
134 Everett DW, Chando TJ, Didonato GC, Singhvi SM, Pan HY, Weinstein SH "Biotransformation of pravastatin sodium in humans." Drug Metab Dispos 19 (1991): 740-8. [PMID: 1680649]
135 Product Information. Olysio (simeprevir). Janssen Pharmaceuticals, Titusville, NJ.
136 Product Information. Vosevi (sofosbuvir/velpatasvir/voxilaprevir). Gilead Sciences, Foster City, CA.
137 Product Information. Accolate (zafirlukast). Zeneca Pharmaceuticals, Wilmington, DE.
138 Product Information. Rukobia (fostemsavir). ViiV Healthcare, Research Triangle Park, NC.
139 Gerber JG, Rosenkranz SL, Fichtenbaum CJ, et al. "Effect of efavirenz on the pharmacokinetics of simvastatin, atorvastatin, and pravastatin: results of AIDS Clinical Trials Group 5108 Study." J Acquir Immune Defic Syndr 39 (2005): 307-12. [PMID: 15980690]
140 Argov Z, Mastaglia FL "Drug-induced peripheral neuropathies." Br Med J 1 (1979): 663-6. [PMID: 219931]
141 Blakely KM, Drucker AM, Rosen CF "Drug-induced photosensitivity-an update: Culprit drugs, prevention and management." Drug Saf 42 (2019): 827-47. [PMID: 30888626]
142 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]
143 Product Information. Zydelig (idelalisib). Gilead Sciences, Foster City, CA.
144 Product Information. Clolar (clofarabine). sanofi-aventis, Bridgewater, NJ.
145 Product Information. ReVia (naltrexone). DuPont Pharmaceuticals, Wilmington, DE.