PROBENECID SODIUM

Details

Stereochemistry	ACHIRAL
Molecular Formula	C13H18NO4S.Na
Molecular Weight	307.341
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[Na+].CCCN(CCC)S(=O)(=O)C1=CC=C(C=C1)C([O-])=O

InChI

InChIKey=QCCCFHDTBTUDEA-UHFFFAOYSA-M

InChI=1S/C13H19NO4S.Na/c1-3-9-14(10-4-2)19(17,18)12-7-5-11(6-8-12)13(15)16;/h5-8H,3-4,9-10H2,1-2H3,(H,15,16);/q;+1/p-1

HIDE SMILES / InChI

Molecular Formula	C13H18NO4S
Molecular Weight	284.351
Charge	-1
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Molecular Formula	Na
Molecular Weight	22.9898
Charge	1
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ae126418-5474-4fbe-b83c-bde8b2b4ae6e

Probenecid is the prototypical uricosuric agent. It inhibits the renal excretion of organic anions and reduces tubular reabsorption of urate. Probenecid has also been used to treat patients with renal impairment, and, because it reduces the renal tubular excretion of other drugs, has been used as an adjunct to antibacterial therapy. Probenecid is used for treatment of the hyperuricemia associated with gout and gouty arthritis. Probenecid is a uricosuric and renal tubular blocking agent. It inhibits the tubular reabsorption of urate, thus increasing the urinary excretion of uric acid and decreasing serum urate levels. Effective uricosuria reduces the miscible urate pool, retards urate deposition, and promotes resorption of urate deposits. Probenecid inhibits the tubular secretion of penicillin and usually increases penicillin plasma levels by any route the antibiotic is given. A 2-fold to 4-fold elevation has been demonstrated for various penicillins. Probenecid decreases both hepatic and renal excretion of sulfobromophthalein (BSP). The tubular reabsorption of phosphorus is inhibited in hypoparathyroid but not in euparathyroid individuals. Probenecid does not influence plasma concentrations of salicylates, nor the excretion of streptomycin, chloramphenicol, chlortetracycline, oxytetracycline, or neomycin.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Solute carrier family 22 member 6 19 Target ID: CHEMBL1641347 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11426832	Inhibitor 8297	12.1 µM [Ki]
Solute carrier family 22 member 8 17 Target ID: CHEMBL1641348 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11426832	Inhibitor 8297	5.6 µM [IC50]
Solute carrier family 22 member 11 12 Target ID: CHEMBL2073677 Sources: https://www.ncbi.nlm.nih.gov/pubmed/?term=12130730	Inhibitor 8297

Conditions

Condition	Modality	Targets	Highest Phase	Product
Gout 28 Sources: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ae126418-5474-4fbe-b83c-bde8b2b4ae6e	Palliative		Approved 8429	PROBENECID Approved Use For treatment of the hyperuricemia associated with gout and gouty arthritis. As an adjuvant to therapy with penicillin or with ampicillin, methicillin, oxacillin, cloxacillin, or nafcillin, for elevation and prolongation of plasma levels by whatever route the antibiotic is given. Launch Date 1983
Gouty arthritis 4 Sources: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ae126418-5474-4fbe-b83c-bde8b2b4ae6e	Palliative		Approved 8429	PROBENECID Approved Use For treatment of the hyperuricemia associated with gout and gouty arthritis. As an adjuvant to therapy with penicillin or with ampicillin, methicillin, oxacillin, cloxacillin, or nafcillin, for elevation and prolongation of plasma levels by whatever route the antibiotic is given. Launch Date 1983

C_max

Value	Dose	Analyte	Population
148.6 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7175716/	2000 mg single, oral dose: 2000 mg route of administration: Oral experiment type: SINGLE co-administered:	PROBENECID plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
35.3 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7175716/	500 mg single, oral dose: 500 mg route of administration: Oral experiment type: SINGLE co-administered:	PROBENECID plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
69.6 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7175716/	1000 mg single, oral dose: 1000 mg route of administration: Oral experiment type: SINGLE co-administered:	PROBENECID plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

AUC

Value	Dose	Analyte	Population
2109 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7175716/	2000 mg single, oral dose: 2000 mg route of administration: Oral experiment type: SINGLE co-administered:	PROBENECID plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
292 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7175716/	500 mg single, oral dose: 500 mg route of administration: Oral experiment type: SINGLE co-administered:	PROBENECID plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
772 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7175716/	1000 mg single, oral dose: 1000 mg route of administration: Oral experiment type: SINGLE co-administered:	PROBENECID plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

T_1/2

Value	Dose	Analyte	Population
8.5 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7175716/	2000 mg single, oral dose: 2000 mg route of administration: Oral experiment type: SINGLE co-administered:	PROBENECID plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
4.2 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7175716/	500 mg single, oral dose: 500 mg route of administration: Oral experiment type: SINGLE co-administered:	PROBENECID plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
4.9 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7175716/	1000 mg single, oral dose: 1000 mg route of administration: Oral experiment type: SINGLE co-administered:	PROBENECID plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inducer 781	inhibitor 1767

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2C19 1478 MRP4 204 UGT 35 MRP1 106 OAT4 146 MRP5 22 OAT2 145 OAT3 642 OAT1 599		CYP2C8 168

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
MRP1 172	inhibitor 3277 Sources: https://bioinformatics.charite.de/transformer/index.php?site=fullinfo&cname=000057669	weak
MRP4 238	inhibitor 3277 Sources: http://transportal.compbio.ucsf.edu/compounds/probenecid/	yes [IC50 100 uM]	yes (co-administration study) Comment: MRP4-expressing V79 vesicles (cholyltaurine); Coadministration of Probenecid (1000 mg QD oral) increased Cefmetazole (5 mg/kg QD IV-infusion (1-hr)) AUC by 1.6-fold. Sources: http://transportal.compbio.ucsf.edu/compounds/probenecid/
OAT3 644	inhibitor 3277 Sources: http://transportal.compbio.ucsf.edu/compounds/probenecid/	yes [IC50 3.1 uM]	yes (co-administration study) Comment: CHO-OAT3 (cimetidine); Coadministration of Probenecid (1000 mg QD oral) increased Dicloxacillin (500 mg SD oral) AUC by 1.9-fold and Cmax by 1.8-fold. Sources: http://transportal.compbio.ucsf.edu/compounds/probenecid/
OAT1 603	inhibitor 3277 Sources: http://transportal.compbio.ucsf.edu/compounds/probenecid/	yes [IC50 3.9 uM]	yes (co-administration study) Comment: CHO-OAT1 (cidofovir); Coadministration of Probenecid (1000 mg QD oral) increased Dicloxacillin (500 mg SD oral) AUC by 1.9-fold and Cmax by 1.8-fold. Sources: http://transportal.compbio.ucsf.edu/compounds/probenecid/
MRP5 48	inhibitor 3277 Sources: http://transportal.compbio.ucsf.edu/compounds/probenecid/	yes [IC50 34 uM]	yes (co-administration study) Comment: MRP5-expressing HEK293 vesicles (carboxydichlorofluorescein); Coadministration of Probenecid (1000 mg QD oral) increased Cefmetazole (2000 mg QD IV-infusion (5 min)) AUC by 1.6-fold. Sources: http://transportal.compbio.ucsf.edu/compounds/probenecid/
OAT4 146	inhibitor 3277 Sources: https://bioinformatics.charite.de/transformer/index.php?site=fullinfo&cname=000057669	yes [Ki 54.9 uM]
OAT2 147	inhibitor 3277 Sources: http://transportal.compbio.ucsf.edu/compounds/probenecid/	yes [Ki 766 uM]	yes (co-administration study) Comment: S2-OAT2 (prostaglandin F2alpha); Coadministration of Probenecid (1000 mg QD oral) increased Dicloxacillin (500 mg SD oral) AUC by 1.9-fold and Cmax by 1.8-fold. Sources: http://transportal.compbio.ucsf.edu/compounds/probenecid/
CYP2C19 1553	inhibitor 3277 Sources: https://bioinformatics.charite.de/transformer/index.php?site=fullinfo&cname=000057669	yes	yes (co-administration study) Comment: Coadministration of Probenecid (1000 mg qid on Day 1, 500 mg qid on Days 2-3, and 500 mg QD on Day 4) increased Naproxen (500 mg QD on Day 4) AUCinf by over 2-fold. Sources: https://bioinformatics.charite.de/transformer/index.php?site=fullinfo&cname=000057669
CYP2C8 965	inducer 1573 Sources: https://bioinformatics.charite.de/transformer/index.php?site=fullinfo&cname=000057669	yes	yes (co-administration study) Comment: Coadministration of Probenecid (500 mg BID X 10 days) decreased Carbamazepine (200 mg QD on Day 6) AUCinf by 18% and increased Cmax by 3% while increased Carbamazepine 10,11-epoxide AUCinf by 35% and Cmax by 47%. Sources: https://bioinformatics.charite.de/transformer/index.php?site=fullinfo&cname=000057669
CYP2C9 1819	inhibitor 3277 Sources: https://bioinformatics.charite.de/transformer/index.php?site=fullinfo&cname=000057669	yes	yes (co-administration study) Comment: Coadministration of Probenecid (1000 mg qid on Day 1, 500 mg qid on Days 2-3, and 500 mg QD on Day 4) increased Naproxen (500 mg QD on Day 4) AUCinf by over 2-fold. Sources: https://bioinformatics.charite.de/transformer/index.php?site=fullinfo&cname=000057669
CYP3A4 1925	inducer 1573 Sources: https://bioinformatics.charite.de/transformer/index.php?site=fullinfo&cname=000057669	yes	yes (co-administration study) Comment: Coadministration of Probenecid (500 mg BID X 10 days) decreased Carbamazepine (200 mg QD on Day 6) AUCinf by 18% and increased Cmax by 3% while increased Carbamazepine 10,11-epoxide AUCinf by 35% and Cmax by 47%. Sources: https://bioinformatics.charite.de/transformer/index.php?site=fullinfo&cname=000057669
UGT 59	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/2570186/	yes	yes (co-administration study) Comment: Coadministration of Probenecid (500 mg q8h X 3 days) increased Zidovudine (q8h x 3 day) AUC by 80%. Sources: https://pubmed.ncbi.nlm.nih.gov/2570186/

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:8426	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:8426
ChemicalBook	CB9134579	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB9134579
MolPort	MolPort-000-145-935	https://www.molport.com/shop/molecule-link/MolPort-000-145-935
Selleck Chemicals	probenecid-benemid	http://www.selleckchem.com/products/probenecid-benemid.html
ZINC	ZINC000000001982	http://zinc15.docking.org/substances/ZINC000000001982
eMolecules	27523493	https://www.emolecules.com/cgi-bin/more?vid=27523493
eMolecules	593868	https://www.emolecules.com/cgi-bin/more?vid=593868

PubMed

Title	Date	PubMed
Studies on the modification of renal lesions due to aspirin and oxyphenbutazone in the rat and the effects on the kidney of 2:4 dinitrophenol.	1976 Jul	1004943
Skin sensitizing properties of arylalcanoic acids and their analogues.	1979 Sep	509935
Treatment of gonorrhea: comparison of cefotaxime and penicillin.	1981 May	6271049
Probenecid induced immune hemolytic anemia.	1986 Feb	3701734
Subjective sensation of heaviness in gout patients.	2000 Jun	10920575
Identification and characterization of human organic anion transporter 3 expressing predominantly in the kidney.	2001 May	11306713
Cidofovir-induced end-stage renal failure.	2002 Jan	11773481
Chronic arsenic-exposed human prostate epithelial cells exhibit stable arsenic tolerance: mechanistic implications of altered cellular glutathione and glutathione S-transferase.	2002 Sep 1	12387749
Functional expression of the multidrug resistance protein 1 in microglia.	2003 Oct	12893836
Identification and functional assessment of the novel murine organic anion transporter Oat5 (Slc22a19) expressed in kidney.	2004 Aug	15068970
Monocarboxylate transport inhibition alters retinal function and cellular amino acid levels.	2004 Sep	15355319
Modulation of MRP1 protein transport by plant, and synthetically modified flavonoids.	2005 Aug 26	15916776
Prediction of genotoxicity of chemical compounds by statistical learning methods.	2005 Jun	15962942
Mrp2/Abcc2 transport activity is stimulated by protein kinase Calpha in a baculo virus co-expression system.	2005 Jun 17	15904671
MRP2 (ABCC2) transports taxanes and confers paclitaxel resistance and both processes are stimulated by probenecid.	2005 Sep 20	15849751
Transport of estrone sulfate by the novel organic anion transporter Oat6 (Slc22a20).	2006 Aug	16478971
One center's experience: the serology and drugs associated with drug-induced immune hemolytic anemia--a new paradigm.	2007 Apr	17381629
Biochemical effectiveness of allopurinol and allopurinol-probenecid in previously benzbromarone-treated gout patients.	2007 Sep	17308859
Transient receptor potential V2 expressed in sensory neurons is activated by probenecid.	2007 Sep 25	17850966
Molecular evidence for an involvement of organic anion transporters (OATs) in aristolochic acid nephropathy.	2009 Oct 1	19643159
Multidrug resistance proteins restrain the intestinal absorption of trans-resveratrol in rats.	2010 Mar	20089784
Interactions of urate transporter URAT1 in human kidney with uricosuric drugs.	2011 Feb	21272127
A correlation between the in vitro drug toxicity of drugs to cell lines that express human P450s and their propensity to cause liver injury in humans.	2014 Jan	24085192

Patents

Sample Use Guides

In Vivo Use Guide

Gout: The recommended adult dosage is 250 mg (1/2 tablet) twice a day for one week, followed by 500 mg (1 tablet) twice a day thereafter.

Route of Administration: Oral

In Vitro Use Guide

Probenecid, at concentrations that had no effect on parasite viability alone (50 uM), was shown to increase the sensitivity of a highly resistant parasite isolate to the antifolates pyrimethamine, sulfadoxine, chlorcycloguanil, and dapsone by seven-, five-, three-, and threefold, respectively. Probenecid decreased the level of uptake of radiolabeled folic acid, suggesting a transport-based mechanism linked to folate salvage.

Substance Class	Chemical Created by `admin` on `Sat Dec 16 03:28:53 GMT 2023` Edited by `admin` on `Sat Dec 16 03:28:53 GMT 2023`
Record UNII	FXB45Q4ZVK
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

PROBENECID SODIUM

Common Name

English

4-((DIPROPYLAMINO)SULFONYL)BENZOIC ACID, SODIUM SALT

Common Name

English

SODIUM 4-((DIPROPYLAMINO)SULFONYL)BENZOATE

Systematic Name

English

PROBENECID SODIUM SALT [MI]

Common Name

English

Code System Code Type Description

EPA CompTox

DTXSID80178478