Details of the Drug

General Information of Drug (ID: DM60QMR)

Drug Name

Ethacrynic acid

Synonyms

Crinuryl; Edecril; Edecrina; Endecril; Ethacrynate; Hidromedin; Hydromedin; Mingit; Otacril; Reomax; Taladren; Uregit; Acide etacrynique; Acido etacrinico; Acidum etacrynicum; Etacrinic acid; Etacrynic Acid; Etakrinic acid; Ethacrinic acid; Ethacryinic Acid; Kyselina ethakrynova; Kyselina ethakrynova [Czech]; Methylenebutyryl phenoxyacetic acid; Methylenebutyrylphenoxyacetic acid; E0526; MK 595; Acide etacrynique [INN-French]; Acido etacrinico [INN-Spanish]; Acidum etacrynicum [INN-Latin]; Edecrin (TN); Ethacrinique (acide); Ethacrynic Acid, Sodium Salt; Ethacrynic acid (USP); Ethacrynic acid [USAN:BAN]; MK-595; Etacrynic acid (JP15/INN); [2,3-Dichloro-4-(2-methylenebutyryl)phenoxy]acetic acid; [2,3-dichloro-4-(2-methylenebutanoyl)phenoxy]acetic acid; [2,3-dichloro-4-(2-methylidenebutanoyl)phenoxy]acetic acid; [4-(2-Methylenebutyryl)-2,3-dichlorophenoxy]acetic acid; Kyselina 4-(2-(1-butenyl)karbonyl)-2,3-dichlorfenoxyoctova; Kyselina 4-(2-(1-butenyl)karbonyl)-2,3-dichlorfenoxyoctova [Czech]; [2,3-Dichloro-4-(2-methylene-1-oxobutyl)phenoxy]acetic acid; (2,3-Dichloro-4-(2-methylene-1-oxobutyl)phenoxy)acetic acid; (2,3-Dichloro-4-(2-methylenebutyryl)phenoxy)acetic acid; (2,3-Dichloro-4-[2-methylenebutyryl]phenoxy)acetic acid; (4-(2-Methylenebutyryl)-2,3-dichlorophenoxy)acetic acid; 2,3-Dichloro-4(2-methylene-butyryl)phenoxy] acetic acid; 2,3-Dichloro-4-(2-methylenebutyl)phenoxyacetic acid; 2,3-Dichloro-4-(2-methylenebutyryl)phenoxy acetic acid; 2,3-Dichloro-4-(2-methylenebutyryl)phenoxyacetic acid; 2-[2,3-dichloro-4-(2-methylidenebutanoyl)phenoxy]acetic acid

Indication

Disease Entry	ICD 11	Status	REF
High blood pressure	BA00	Approved	[1], [2]

Therapeutic Class

Diuretics

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 0

Molecular Weight (mw)

303.13

Topological Polar Surface Area (xlogp)

3.8

Rotatable Bond Count (rotbonds)

Hydrogen Bond Donor Count (hbonddonor)

Hydrogen Bond Acceptor Count (hbondacc)

ADMET Property

Bioavailability: 99% of drug becomes completely available to its intended biological destination(s) [3]
Clearance: The drug present in the plasma can be removed from the body at the rate of 8.7 mL/min/kg [4]
Half-life: The concentration or amount of drug in body reduced by one-half in 0.5 hours [4]
Metabolism: The drug is metabolized via the hepatic [5]
MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 4.7126 micromolar/kg/day [6]
Vd: Fluid volume that would be required to contain the amount of drug present in the body at the same concentration as in the plasma 0.26 L/kg [4]

Chemical Identifiers

Formula: C13H12Cl2O4
IUPAC Name: 2-[2,3-dichloro-4-(2-methylidenebutanoyl)phenoxy]acetic acid
Canonical SMILES: CCC(=C)C(=O)C1=C(C(=C(C=C1)OCC(=O)O)Cl)Cl
InChI: InChI=1S/C13H12Cl2O4/c1-3-7(2)13(18)8-4-5-9(12(15)11(8)14)19-6-10(16)17/h4-5H,2-3,6H2,1H3,(H,16,17)
InChIKey: AVOLMBLBETYQHX-UHFFFAOYSA-N

Cross-matching ID

PubChem CID: 3278
ChEBI ID: CHEBI:4876
CAS Number: 58-54-8
DrugBank ID: DB00903
TTD ID: D06TNL
VARIDT ID: DR00548
INTEDE ID: DR0653
ACDINA ID: D00251

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Solute carrier family 12 member 1 (SLC12A1)	TTS087L	S12A1_HUMAN	Blocker	[7], [8]

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Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
Multidrug resistance-associated protein 1 (ABCC1)	DTSYQGK	MRP1_HUMAN	Substrate	[9]

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Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 1A1 (CYP1A1)	DE6OQ3W	CP1A1_HUMAN	Substrate	[10]
Glutathione S-transferase alpha-1 (GSTA1)	DE4ZHS1	GSTA1_HUMAN	Substrate	[11]

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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This Drug

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Ethacrynic acid (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Cefuroxime	DMSIMD8	Moderate	Increased renal excretion of Ethacrynic acid caused by Cefuroxime.	Acute bronchitis [CA42]	[50]
Cefamandole	DMNEXZF	Moderate	Increased renal excretion of Ethacrynic acid caused by Cefamandole.	Anaerobic bacterial infection [1A00-1A09]	[50]
Dronedarone	DMA8FS5	Major	Increased risk of ventricular arrhythmias by the combination of Ethacrynic acid and Dronedarone.	Angina pectoris [BA40]	[51]
Cefotetan	DM07TX3	Moderate	Increased renal excretion of Ethacrynic acid caused by Cefotetan.	Bacterial infection [1A00-1C4Z]	[50]
Kanamycin	DM2DMPO	Major	Increased risk of ototoxicity by the combination of Ethacrynic acid and Kanamycin.	Bacterial infection [1A00-1C4Z]	[52]
Ceftizoxime	DM3VOGS	Moderate	Increased renal excretion of Ethacrynic acid caused by Ceftizoxime.	Bacterial infection [1A00-1C4Z]	[50]
Cefoperazone	DM53PV8	Moderate	Increased renal excretion of Ethacrynic acid caused by Cefoperazone.	Bacterial infection [1A00-1C4Z]	[50]
Cefprozil	DM7DSYP	Moderate	Increased renal excretion of Ethacrynic acid caused by Cefprozil.	Bacterial infection [1A00-1C4Z]	[50]
Ceftriaxone	DMCEW64	Moderate	Increased renal excretion of Ethacrynic acid caused by Ceftriaxone.	Bacterial infection [1A00-1C4Z]	[50]
Streptomycin	DME1LQN	Major	Increased risk of ototoxicity by the combination of Ethacrynic acid and Streptomycin.	Bacterial infection [1A00-1C4Z]	[52]
Cefepime	DMHVWIK	Moderate	Increased renal excretion of Ethacrynic acid caused by Cefepime.	Bacterial infection [1A00-1C4Z]	[50]
Cefpodoxime	DMJUNY5	Moderate	Increased renal excretion of Ethacrynic acid caused by Cefpodoxime.	Bacterial infection [1A00-1C4Z]	[50]
Cefadroxil	DMMC345	Moderate	Increased renal excretion of Ethacrynic acid caused by Cefadroxil.	Bacterial infection [1A00-1C4Z]	[50]
Rabeprazole	DMMZXIW	Moderate	Increased risk of hypomagnesemia by the combination of Ethacrynic acid and Rabeprazole.	Bacterial infection [1A00-1C4Z]	[53]
Netilmicin	DMRD1QK	Major	Increased risk of nephrotoxicity by the combination of Ethacrynic acid and Netilmicin.	Bacterial infection [1A00-1C4Z]	[52]
Cefditoren	DMSUVM1	Moderate	Increased renal excretion of Ethacrynic acid caused by Cefditoren.	Bacterial infection [1A00-1C4Z]	[50]
Cefonicid	DMTX2BH	Moderate	Increased renal excretion of Ethacrynic acid caused by Cefonicid.	Bacterial infection [1A00-1C4Z]	[50]
Cefradine	DMUNSWV	Moderate	Increased renal excretion of Ethacrynic acid caused by Cefradine.	Bacterial infection [1A00-1C4Z]	[50]
Cefoxitin	DMYTXVR	Moderate	Increased renal excretion of Ethacrynic acid caused by Cefoxitin.	Bacterial infection [1A00-1C4Z]	[50]
Cariprazine	DMJYDVK	Moderate	Additive hypotensive effects by the combination of Ethacrynic acid and Cariprazine.	Bipolar disorder [6A60]	[54]
Etidronic acid	DM1XHYJ	Moderate	Increased risk of hypocalcemia by the combination of Ethacrynic acid and Etidronic acid.	Bone paget disease [FB85]	[55]
Ceftibuten	DMWV2AG	Moderate	Increased renal excretion of Ethacrynic acid caused by Ceftibuten.	Bronchitis [CA20]	[50]
Ketoprofen	DMRKXPT	Moderate	Antagonize the effect of Ethacrynic acid when combined with Ketoprofen.	Chronic pain [MG30]	[56]
Levomilnacipran	DMV26S8	Moderate	Increased risk of hyponatremia by the combination of Ethacrynic acid and Levomilnacipran.	Chronic pain [MG30]	[57]
Sertraline	DM0FB1J	Moderate	Increased risk of hyponatremia by the combination of Ethacrynic acid and Sertraline.	Depression [6A70-6A7Z]	[57]
Vilazodone	DM4LECQ	Moderate	Increased risk of hyponatremia by the combination of Ethacrynic acid and Vilazodone.	Depression [6A70-6A7Z]	[57]
Selegiline	DM6034S	Moderate	Additive hypotensive effects by the combination of Ethacrynic acid and Selegiline.	Depression [6A70-6A7Z]	[58]
Vortioxetine	DM6F1PU	Moderate	Increased risk of hyponatremia by the combination of Ethacrynic acid and Vortioxetine.	Depression [6A70-6A7Z]	[57]
Isocarboxazid	DMAF1NB	Moderate	Additive hypotensive effects by the combination of Ethacrynic acid and Isocarboxazid.	Depression [6A70-6A7Z]	[58]
Milnacipran	DMBFE74	Moderate	Increased risk of hyponatremia by the combination of Ethacrynic acid and Milnacipran.	Depression [6A70-6A7Z]	[57]
Escitalopram	DMFK9HG	Moderate	Increased risk of hyponatremia by the combination of Ethacrynic acid and Escitalopram.	Depression [6A70-6A7Z]	[57]
OPC-34712	DMHG57U	Moderate	Additive hypotensive effects by the combination of Ethacrynic acid and OPC-34712.	Depression [6A70-6A7Z]	[54]
Eslicarbazepine	DMZREFQ	Moderate	Increased risk of hyponatremia by the combination of Ethacrynic acid and Eslicarbazepine.	Epilepsy/seizure [8A61-8A6Z]	[59]
Dexlansoprazole	DM1DBV5	Moderate	Increased risk of hypomagnesemia by the combination of Ethacrynic acid and Dexlansoprazole.	Gastro-oesophageal reflux disease [DA22]	[53]
Metipranolol	DMJMVKI	Moderate	Increased risk of hyperglycemia by the combination of Ethacrynic acid and Metipranolol.	Glaucoma [9C61]	[60]
Levobetaxolol	DMSREPX	Moderate	Increased risk of hyperglycemia by the combination of Ethacrynic acid and Levobetaxolol.	Glaucoma [9C61]	[60]
Levobunolol	DMTNFCQ	Moderate	Increased risk of hypertriglyceridemia by the combination of Ethacrynic acid and Levobunolol.	Glaucoma [9C61]	[60]
Carvedilol	DMHTEAO	Moderate	Increased risk of ventricular arrhythmias by the combination of Ethacrynic acid and Carvedilol.	Heart failure [BD10-BD1Z]	[60]
Digitoxin	DMWVIGP	Moderate	Increased risk of hypomagnesemia by the combination of Ethacrynic acid and Digitoxin.	Heart failure [BD10-BD1Z]	[61]
Procarbazine	DMIK367	Moderate	Additive hypotensive effects by the combination of Ethacrynic acid and Procarbazine.	Hodgkin lymphoma [2B30]	[58]
Etelcalcetide	DMHP9BL	Major	Increased risk of hypocalcemia by the combination of Ethacrynic acid and Etelcalcetide.	Hyper-parathyroidism [5A51]	[62]
Acebutolol	DM0TI4U	Moderate	Increased risk of hyperglycemia by the combination of Ethacrynic acid and Acebutolol.	Hypertension [BA00-BA04]	[60]
Captopril	DM458UM	Moderate	Additive hypotensive effects by the combination of Ethacrynic acid and Captopril.	Hypertension [BA00-BA04]	[63]
Penbutolol	DM4ES8F	Moderate	Increased risk of hyperglycemia by the combination of Ethacrynic acid and Penbutolol.	Hypertension [BA00-BA04]	[60]
Nebivolol	DM7F1PA	Moderate	Increased risk of ventricular arrhythmias by the combination of Ethacrynic acid and Nebivolol.	Hypertension [BA00-BA04]	[60]
Pindolol	DMD2NV7	Moderate	Increased risk of hypertriglyceridemia by the combination of Ethacrynic acid and Pindolol.	Hypertension [BA00-BA04]	[60]
Trichlormethiazide	DMHAQCO	Moderate	Increased risk of fluid/electrolyte loss by the combination of Ethacrynic acid and Trichlormethiazide.	Hypertension [BA00-BA04]	[64]
Hydrochlorothiazide	DMUSZHD	Moderate	Increased risk of fluid/electrolyte loss by the combination of Ethacrynic acid and Hydrochlorothiazide.	Hypertension [BA00-BA04]	[64]
Meclofenamic acid	DM05FXR	Moderate	Antagonize the effect of Ethacrynic acid when combined with Meclofenamic acid.	Inflammatory spondyloarthritis [FA92]	[56]
ITI-007	DMUQ1DO	Moderate	Additive hypotensive effects by the combination of Ethacrynic acid and ITI-007.	Insomnia [7A00-7A0Z]	[54]
Arsenic trioxide	DM61TA4	Major	Increased risk of ventricular arrhythmias by the combination of Ethacrynic acid and Arsenic trioxide.	Mature B-cell lymphoma [2A85]	[65]
Ozanimod	DMT6AM2	Moderate	Additive hypotensive effects by the combination of Ethacrynic acid and Ozanimod.	Multiple sclerosis [8A40]	[58]
Promethazine	DM6I5GR	Moderate	Additive hypotensive effects by the combination of Ethacrynic acid and Promethazine.	Nausea/vomiting [MD90]	[54]
Sibutramine	DMFJTDI	Moderate	Increased risk of hyponatremia by the combination of Ethacrynic acid and Sibutramine.	Obesity [5B80-5B81]	[57]
Polythiazide	DMCH80F	Moderate	Increased risk of fluid/electrolyte loss by the combination of Ethacrynic acid and Polythiazide.	Oedema [MG29]	[64]
Levomethadyl Acetate	DM06HG5	Major	Increased risk of ventricular arrhythmias by the combination of Ethacrynic acid and Levomethadyl Acetate.	Opioid use disorder [6C43]	[66]
Carboplatin	DMG281S	Moderate	Increased risk of ototoxicity by the combination of Ethacrynic acid and Carboplatin.	Ovarian cancer [2C73]	[67]
Ibuprofen	DM8VCBE	Moderate	Antagonize the effect of Ethacrynic acid when combined with Ibuprofen.	Pain [MG30-MG3Z]	[56]
Safinamide	DM0YWJC	Moderate	Additive hypotensive effects by the combination of Ethacrynic acid and Safinamide.	Parkinsonism [8A00]	[58]
Rasagiline	DM3WKQ4	Moderate	Additive hypotensive effects by the combination of Ethacrynic acid and Rasagiline.	Parkinsonism [8A00]	[58]
Bromfenac	DMKB79O	Moderate	Antagonize the effect of Ethacrynic acid when combined with Bromfenac.	Postoperative inflammation [1A00-CA43]	[56]
Levomepromazine	DMIKFEL	Moderate	Additive hypotensive effects by the combination of Ethacrynic acid and Levomepromazine.	Psychotic disorder [6A20-6A25]	[54]
Oxaprozin	DM9UB0P	Moderate	Antagonize the effect of Ethacrynic acid when combined with Oxaprozin.	Rheumatoid arthritis [FA20]	[56]
Quetiapine	DM1N62C	Moderate	Additive hypotensive effects by the combination of Ethacrynic acid and Quetiapine.	Schizophrenia [6A20]	[54]
Mesoridazine	DM2ZGAN	Moderate	Additive hypotensive effects by the combination of Ethacrynic acid and Mesoridazine.	Schizophrenia [6A20]	[54]
Aripiprazole	DM3NUMH	Moderate	Additive hypotensive effects by the combination of Ethacrynic acid and Aripiprazole.	Schizophrenia [6A20]	[54]
Iloperidone	DM6AUFY	Moderate	Increased risk of ventricular arrhythmias by the combination of Ethacrynic acid and Iloperidone.	Schizophrenia [6A20]	[68]
Paliperidone	DM7NPJS	Moderate	Increased risk of ventricular arrhythmias by the combination of Ethacrynic acid and Paliperidone.	Schizophrenia [6A20]	[68]
Molindone	DMAH70G	Moderate	Additive hypotensive effects by the combination of Ethacrynic acid and Molindone.	Schizophrenia [6A20]	[54]
Thiothixene	DMDINC4	Moderate	Additive hypotensive effects by the combination of Ethacrynic acid and Thiothixene.	Schizophrenia [6A20]	[54]
Amisulpride	DMSJVAM	Moderate	Additive hypotensive effects by the combination of Ethacrynic acid and Amisulpride.	Schizophrenia [6A20]	[54]
Asenapine	DMSQZE2	Moderate	Additive hypotensive effects by the combination of Ethacrynic acid and Asenapine.	Schizophrenia [6A20]	[54]
Pimozide	DMW83TP	Major	Increased risk of ventricular arrhythmias by the combination of Ethacrynic acid and Pimozide.	Schizophrenia [6A20]	[69]
Cephapirin	DMV2JNY	Moderate	Increased renal excretion of Ethacrynic acid caused by Cephapirin.	Sepsis [1G40-1G41]	[50]
Plazomicin	DMKMBES	Major	Increased risk of ototoxicity by the combination of Ethacrynic acid and Plazomicin.	Urinary tract infection [GC08]	[52]
Trimeprazine	DMEMV9D	Moderate	Additive hypotensive effects by the combination of Ethacrynic acid and Trimeprazine.	Vasomotor/allergic rhinitis [CA08]	[54]
Amiodarone	DMUTEX3	Major	Increased risk of ventricular arrhythmias by the combination of Ethacrynic acid and Amiodarone.	Ventricular tachyarrhythmia [BC71]	[70]
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⏷ Show the Full List of 77 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
Beta-D-lactose	E00099	6134	Diluent; Dry powder inhaler carrier; Lyophilization aid
Calcium stearate	E00244	15324	lubricant
Lactose monohydrate	E00393	104938	Binding agent; Diluent; Dry powder inhaler carrier; Lyophilization aid
Magnesium stearate	E00208	11177	lubricant
Silicon dioxide	E00670	Not Available	Anticaking agent; Opacifying agent; Viscosity-controlling agent
Talc	E00520	16211421	Anticaking agent; Diluent; Glidant; lubricant
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⏷ Show the Full List of 6 Pharmaceutical Excipients of This Drug

Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Ethacrynic acid 25 mg tablet	25 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: 7179).
2	FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 016092.
3	Critical Evaluation of Human Oral Bioavailability for Pharmaceutical Drugs by Using Various Cheminformatics Approaches
4	Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
5	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.
6	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
7	Na-K-Cl cotransport regulates intracellular volume and monolayer permeability of trabecular meshwork cells. Am J Physiol. 1995 Apr;268(4 Pt 1):C1067-74.
8	Inhibition of Na-K-2Cl cotransport and bumetanide binding by ethacrynic acid, its analogues, and adducts. Am J Physiol. 1993 May;264(5 Pt 1):C1270-7.
9	Inhibition of the multidrug resistance protein 1 (MRP1) by peptidomimetic glutathione-conjugate analogs. Mol Pharmacol. 2002 Nov;62(5):1160-6.
10	Xenobiotic metabolizing and antioxidant enzymes in normal and neoplastic human breast tissue. Eur J Drug Metab Pharmacokinet. 1998 Oct-Dec;23(4):497-500.
11	Purification and biochemical properties of glutathione S-transferase from Lactuca sativa. J Biochem Mol Biol. 2005 Mar 31;38(2):232-7.
12	Allelic variants of human cytochrome P450 1A1 (CYP1A1): effect of T461N and I462V substitutions on steroid hydroxylase specificity. Pharmacogenetics. 2000 Aug;10(6):519-30.
13	Metabolism of tamoxifen by recombinant human cytochrome P450 enzymes: formation of the 4-hydroxy, 4'-hydroxy and N-desmethyl metabolites and isomerization of trans-4-hydroxytamoxifen. Drug Metab Dispos. 2002 Aug;30(8):869-74.
14	Cytochrome P450 isoforms catalyze formation of catechol estrogen quinones that react with DNA. Metabolism. 2007 Jul;56(7):887-94.
15	Preferred orientations in the binding of 4'-hydroxyacetanilide (acetaminophen) to cytochrome P450 1A1 and 2B1 isoforms as determined by 13C- and 15N-NMR relaxation studies. J Med Chem. 1994 Mar 18;37(6):860-7.
16	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.
17	Diclofenac and its derivatives as tools for studying human cytochromes P450 active sites: particular efficiency and regioselectivity of P450 2Cs. Biochemistry. 1999 Oct 26;38(43):14264-70.
18	A common CYP1B1 polymorphism is associated with 2-OHE1/16-OHE1 urinary estrone ratio. Clin Chem Lab Med. 2005;43(7):702-6.
19	Cytochromes P450 in crustacea. Comp Biochem Physiol C Pharmacol Toxicol Endocrinol. 1998 Nov;121(1-3):157-72.
20	Disruption of endogenous regulator homeostasis underlies the mechanism of rat CYP1A1 mRNA induction by metyrapone. Biochem J. 1998 Apr 1;331 ( Pt 1):273-81.
21	Pharmacogenomics in drug-metabolizing enzymes catalyzing anticancer drugs for personalized cancer chemotherapy. Curr Drug Metab. 2007 Aug;8(6):554-62.
22	Role of glutathione S-transferase P1-1 in the cellular detoxification of cisplatin. Mol Cancer Ther. 2008 Oct;7(10):3247-55.
23	Human glutathione transferase A3-3, a highly efficient catalyst of double-bond isomerization in the biosynthetic pathway of steroid hormones. J Biol Chem. 2001 Aug 31;276(35):33061-5.
24	Retinoid X receptor alpha regulates the expression of glutathione s-transferase genes and modulates acetaminophen-glutathione conjugation in mouse liver. Mol Pharmacol. 2005 Dec;68(6):1590-6.
25	Comparison of basal glutathione S-transferase activities and of the influence of phenobarbital, butylated hydroxy-anisole or 5,5'-diphenylhydantoin on enzyme activity in male rodents. Comp Biochem Physiol C. 1987;88(1):91-3.
26	Characterization and formation of the glutathione conjugate of clofibric acid. Drug Metab Dispos. 1995 Jan;23(1):119-23.
27	In vitro characterization of the human biotransformation and CYP reaction phenotype of ET-743 (Yondelis, Trabectidin), a novel marine anti-cancer drug. Invest New Drugs. 2006 Jan;24(1):3-14.
28	Glutathione S-transferase M1 polymorphism: a risk factor for hepatic venoocclusive disease in bone marrow transplantation. Blood. 2004 Sep 1;104(5):1574-7.
29	Inhibition of glutathione S-transferases by antimalarial drugs possible implications for circumventing anticancer drug resistance. Int J Cancer. 2002 Feb 10;97(5):700-5.
30	Combined glutathione-S-transferase M1 and T1 genetic polymorphism and tacrine hepatotoxicity. Clin Pharmacol Ther. 2000 Apr;67(4):432-7.
31	Metabolism of melphalan by rat liver microsomal glutathione S-transferase. Chem Biol Interact. 2005 Apr 15;152(2-3):101-6.
32	The role of bioreductive activation of doxorubicin in cytotoxic activity against leukaemia HL60-sensitive cell line and its multidrug-resistant sublines. Br J Cancer. 2005 Jul 11;93(1):89-97.
33	Transport of methotrexate (MTX) and folates by multidrug resistance protein (MRP) 3 and MRP1: effect of polyglutamylation on MTX transport. Cancer Res. 2001 Oct 1;61(19):7225-32.
34	Folate concentration dependent transport activity of the Multidrug Resistance Protein 1 (ABCC1). Biochem Pharmacol. 2004 Apr 15;67(8):1541-8.
35	Hammerhead ribozyme against gamma-glutamylcysteine synthetase sensitizes human colonic cancer cells to cisplatin by down-regulating both the glutathione synthesis and the expression of multidrug resistance proteins. Cancer Gene Ther. 2001 Oct;8(10):803-14.
36	Multidrug resistance-associated protein-1 functional activity in Calu-3 cells. J Pharmacol Exp Ther. 2001 Sep;298(3):1199-205.
37	Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
38	ATP-Dependent efflux of CPT-11 and SN-38 by the multidrug resistance protein (MRP) and its inhibition by PAK-104P. Mol Pharmacol. 1999 May;55(5):921-8.
39	Structural determinants of substrate specificity differences between human multidrug resistance protein (MRP) 1 (ABCC1) and MRP3 (ABCC3). Drug Metab Dispos. 2008 Dec;36(12):2571-81.
40	Evaluation of transport of common antiepileptic drugs by human multidrug resistance-associated proteins (MRP1, 2 and 5) that are overexpressed in pharmacoresistant epilepsy. Neuropharmacology. 2010 Jun;58(7):1019-32.
41	Vinblastine and sulfinpyrazone export by the multidrug resistance protein MRP2 is associated with glutathione export. Br J Cancer. 2000 Aug;83(3):375-83.
42	Nongenomic effect of aldosterone on ion transport pathways of red blood cells. Cell Physiol Biochem. 2008;22(1-4):269-78.
43	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
44	Update of diuretics in the treatment of hypertension. Am J Ther. 2007 Mar-Apr;14(2):154-60.
45	Nerve Terminal GABAA Receptors Activate Ca2+/Calmodulin-dependent Signaling to Inhibit Voltage-gated Ca2+ Influx and Glutamate Release. J Biol Chem. 2009 Mar 27;284(13):8726-37.
46	Genetic variation in the renal sodium transporters NKCC2, NCC, and ENaC in relation to the effects of loop diuretic drugs. Clin Pharmacol Ther. 2007 Sep;82(3):300-9.
47	DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6.
48	Function and regulation of epithelial sodium transporters in the kidney of a salt-sensitive hypertensive rat model. J Hypertens. 2007 May;25(5):1065-72.
49	The 45-year story of the development of an anti-aldosterone more specific than spironolactone. Mol Cell Endocrinol. 2004 Mar 31;217(1-2):45-52.
50	Chrysos G, Gargalianos P, Lelekis M, Stefanou J, Kosmidis J "Pharmacokinetic interactions of ceftazidime and frusemide." J Chemother 7 Suppl (1995): 107-10. [PMID: 8904125]
51	Product Information. Multaq (dronedarone). sanofi-aventis , Bridgewater, NJ.
52	Bates DE, Beaumont SJ, Baylis BW "Ototoxicity induced by gentamicin and furosemide." Ann Pharmacother 36 (2002): 446-51. [PMID: 11895059]
53	Product Information. Nexium (esomeprazole) Astra-Zeneca Pharmaceuticals, Wilmington, DE.
54	Product Information. Clozaril (clozapine). Novartis Pharmaceuticals, East Hanover, NJ.
55	Product Information. Skelid (tilundronate). Sanofi Winthrop Pharmaceuticals, New York, NY.
56	Muller FO, Schall R, Devaal AC, Groenewoud G, Hundt HKL, Middle MV "Influence of meloxicam on furosemide pharmacokinetics and pharmacodynamics in healthy volunteers." Eur J Clin Pharmacol 48 (1995): 247-51. [PMID: 7589049]
57	Product Information. Savella (milnacipran). Forest Pharmaceuticals, St. Louis, MO.
58	Product Information. Marplan (isocarboxazid) Roche Laboratories, Nutley, NJ.
59	Product Information. Aptiom (eslicarbazepine). Sunovion Pharmaceuticals Inc, Marlborough, MA.
60	Dean S, Kendall MJ, Potter S, Thompson MH, Jackson DA "Nadolol in combination with indapamide and xipamide in resistant hypertensives." Eur J Clin Pharmacol 28 (1985): 29-33. [PMID: 3987783]
61	Semple P, Tilstone WJ, Lawson DH "Furosemide and urinary digoxin clearance." N Engl J Med 293 (1975): 612-3. [PMID: 902451]
62	Cerner Multum, Inc. "UK Summary of Product Characteristics.".
63	Murphy BF, Whitworth JA, Kincaid-Smith P "Renal insufficiency with combinations of angiotensin converting enzyme inhibitors and diuretics." Br Med J 288 (1984): 844-5. [PMID: 6322905]
64	Leary WP, Reyes AJ "Drug interactions with diuretics." S Afr Med J 65 (1984): 455-61. [PMID: 6701709]
65	Ohnishi K, Yoshida H, Shigeno K, et al. "Prolongation of the QT interval and ventricular tachycardia in patients treated with arsenic trioxide for acute promyelocytic leukemia." Ann Intern Med 133 (2000): 881-5. [PMID: 11103058]
66	Cohen J "Long-term efficacy and safety of terazosin alone and in combination with other antihypertensive agents." Am Heart J 122 (1991): 919-25. [PMID: 1678923]
67	Langer T, am Zehnhoff-Dinnesen A, Radtke S, Meitert J, Zolk O "Understanding platinum-induced ototoxicity." Trends Pharmacol Sci 34 (2013): 458-69. [PMID: 23769626]
68	Cerner Multum, Inc. "Australian Product Information.".
69	Dresser GK, Spence JD, Bailey DG "Pharmacokinetic-pharmacodynamic consequences and clinical relevance of cytochrome P450 3A4 inhibition." Clin Pharmacokinet 38 (2000): 41-57. [PMID: 10668858]
70	Antonelli D, Atar S, Freedberg NA, Rosenfeld T "Torsade de pointes in patients on chronic amiodarone treatment: contributing factors and drug interactions." Isr Med Assoc J 7 (2005): 163-5. [PMID: 15792261]