U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ACHIRAL
Molecular Formula C13H19NO4S
Molecular Weight 285.359
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of PROBENECID

SMILES

CCCN(CCC)S(=O)(=O)C1=CC=C(C=C1)C(O)=O

InChI

InChIKey=DBABZHXKTCFAPX-UHFFFAOYSA-N
InChI=1S/C13H19NO4S/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)

HIDE SMILES / InChI

Molecular Formula C13H19NO4S
Molecular Weight 285.359
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

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

Curator's Comment: After the incidental finding that caronamide, had a uricosuric action (Wolfson and others, 1948), Boger and others (1950) showed that p-(di-n-propylsulphamyl)-benzoic acid (probenecid, 'Benemid') had a similar and more potent effect, and appeared to be less toxic (Boger and Crosson, 1950).

Approval Year

Targets

Targets

Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Palliative
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

4.17743995E11
Palliative
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

4.17743995E11
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
148.6 μg/mL
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
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
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

AUC

ValueDoseCo-administeredAnalytePopulation
2109 μg × h/mL
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
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
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
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
8.5 h
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
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
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

Overview

CYP3A4CYP2C9CYP2D6hERG


OverviewOther

Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
weak
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.
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.
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.
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.
yes [Ki 54.9 uM]
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.
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.
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%.
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.
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%.
yes
yes (co-administration study)
Comment: Coadministration of Probenecid (500 mg q8h X 3 days) increased Zidovudine (q8h x 3 day) AUC by 80%.
PubMed

PubMed

TitleDatePubMed
Nephrotic syndrome caused by probenecid.
1967 Jan 2
Penicillin-induced haemolytic anaemia.
1968 Sep 7
Probenecid-induced nephrotic syndrome.
1972 Sep
Acute Heinz-body anaemia in burned patients.
1973 Sep 1
Letter: Drug-induced red cell aplasia.
1974 Oct 19
Treatment of gonorrhea: comparison of cefotaxime and penicillin.
1981 May
Effect of probenecid on the natriuresis and renin release induced by bumetanide in man.
1981 Nov-Dec
One gram of cefoxitin cures uncomplicated gonococcal urethritis caused by penicillinase-producing Neisseria gonorrhoeae (PPNG).
1983 Jul-Sep
Enhancement of cisplatin nephrotoxicity by probenecid.
1984 Feb
Mechanism of S-(1,2-dichlorovinyl)glutathione-induced nephrotoxicity.
1986 Jan 15
The mechanisms of target cell injury by nephrotoxins.
1986 Jun-Jul
In vivo nephrotoxic action of an isomeric mixture of S-(1-phenyl-2-hydroxyethyl)glutathione and S-(2-phenyl-2-hydroxyethyl)glutathione in Fischer-344 rats.
1991 Mar 25
ATP binding cassette multidrug transporters limit the anti-HIV activity of zidovudine and indinavir in infected human macrophages.
2004 Aug
Carrier-mediated uptake of H2-receptor antagonists by the rat choroid plexus: involvement of rat organic anion transporter 3.
2004 Sep
Expression and activity of multidrug resistance protein 1 in a murine thymoma cell line.
2005 Apr
Biotin uptake by human proximal tubular epithelial cells: cellular and molecular aspects.
2005 Apr
Role of two adjacent cytoplasmic tyrosine residues in MRP1 (ABCC1) transport activity and sensitivity to sulfonylureas.
2005 Feb 1
The outcome of oropharyngeal gonorrhoea treatment with different regimens.
2005 Jan
Mercury induces multidrug resistance-associated protein gene through p38 mitogen-activated protein kinase.
2005 Jan 15
Prediction of genotoxicity of chemical compounds by statistical learning methods.
2005 Jun
Functional characterization of rat organic anion transporter 5 (Slc22a19) at the apical membrane of renal proximal tubules.
2005 Nov
Wartime tactic doubles power of scarce bird-flu drug.
2005 Nov 3
A species difference in the transport activities of H2 receptor antagonists by rat and human renal organic anion and cation transporters.
2005 Oct
MRP2 (ABCC2) transports taxanes and confers paclitaxel resistance and both processes are stimulated by probenecid.
2005 Sep 20
Uric acid causes vascular smooth muscle cell proliferation by entering cells via a functional urate transporter.
2005 Sep-Oct
Inhibition of MRP1-mediated efflux in human erythrocytes by mono-anionic bile salts.
2005 Sep-Oct
Membrane transporter proteins: a challenge for CNS drug development.
2006
A concise history of gout and hyperuricemia and their treatment.
2006
Transport of estrone sulfate by the novel organic anion transporter Oat6 (Slc22a20).
2006 Aug
Is the monkey an appropriate animal model to examine drug-drug interactions involving renal clearance? Effect of probenecid on the renal elimination of H2 receptor antagonists.
2006 Mar
Inhibitory effects of angiotensin II receptor antagonists and leukotriene receptor antagonists on the transport of human organic anion transporter 4.
2006 Nov
Use of immortalized human hepatocytes to predict the magnitude of clinical drug-drug interactions caused by CYP3A4 induction.
2006 Oct
One center's experience: the serology and drugs associated with drug-induced immune hemolytic anemia--a new paradigm.
2007 Apr
In silico prediction of pregnane X receptor activators by machine learning approaches.
2007 Jan
Carboxylic acid drug-induced DNA nicking in HEK293 cells expressing human UDP-glucuronosyltransferases: role of acyl glucuronide metabolites and glycation pathways.
2007 Oct
Biochemical effectiveness of allopurinol and allopurinol-probenecid in previously benzbromarone-treated gout patients.
2007 Sep
Transient receptor potential V2 expressed in sensory neurons is activated by probenecid.
2007 Sep 25
Membrane Based Measurement Technology for in situ Monitoring of Gases in Soil.
2009
Neuroprotective effect of long-term NDI1 gene expression in a chronic mouse model of Parkinson disorder.
2009 Aug
Effects of endurance exercise on ventral tegmental area neurons in the chronic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and probenecid-treated mice.
2009 Jan 30
Detection of HER-2/neu, c-myc amplification and p53 inactivation by FISH in Egyptian patients with breast cancer.
2009 May 6
Pannexin 1 contributes to ATP release in airway epithelia.
2009 Nov
Molecular evidence for an involvement of organic anion transporters (OATs) in aristolochic acid nephropathy.
2009 Oct 1
Multidrug resistance proteins restrain the intestinal absorption of trans-resveratrol in rats.
2010 Mar
Biliary efflux transporters involved in the clearance of rosuvastatin in sandwich culture of primary rat hepatocytes.
2010 Mar
Characterization of cellular uptake of perfluorooctanoate via organic anion-transporting polypeptide 1A2, organic anion transporter 4, and urate transporter 1 for their potential roles in mediating human renal reabsorption of perfluorocarboxylates.
2010 Oct
Targeting organic anion transporter 3 with probenecid as a novel anti-influenza a virus strategy.
2013 Jan
Interactions with selected drug renal transporters and transporter-mediated cytotoxicity in antiviral agents from the group of acyclic nucleoside phosphonates.
2013 Sep 15
Neuroprotective effect of the chemical chaperone, trehalose in a chronic MPTP-induced Parkinson's disease mouse model.
2014 Sep
Novel para-phenyl substituted diindolylmethanes protect against MPTP neurotoxicity and suppress glial activation in a mouse model of Parkinson's disease.
2015 Feb
Patents

Sample Use Guides

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
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 Wed Jul 05 22:51:50 UTC 2023
Edited
by admin
on Wed Jul 05 22:51:50 UTC 2023
Record UNII
PO572Z7917
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
PROBENECID
EP   HSDB   INN   JAN   MART.   MI   ORANGE BOOK   USP   USP-RS   VANDF   WHO-DD   WHO-IP  
INN  
Official Name English
PROBENECID [USP-RS]
Common Name English
PROBAMPACIN COMPONENT PROBENECID
Common Name English
PROBENECID [ORANGE BOOK]
Common Name English
PROBENECID [MART.]
Common Name English
PROBENECID [USP IMPURITY]
Common Name English
PROBENECID [EP MONOGRAPH]
Common Name English
PROBENECID [USP MONOGRAPH]
Common Name English
PROBENATE
Common Name English
BENZOIC ACID, 4-((DIPROPYLAMINO)SULFONYL)-
Common Name English
PROBENECID [JAN]
Common Name English
PROBENECID COMPONENT OF COLBENEMID
Common Name English
probenecid [INN]
Common Name English
PROBENECID COMPONENT OF PROBAMPACIN
Common Name English
PROBENECID COMPONENT OF COL-PROBENECID
Common Name English
P-(DIPROPYLSULFAMOYL)BENZOIC ACID
Common Name English
PROBENECID [MI]
Common Name English
BENEMID
Brand Name English
PROBENECID [HSDB]
Common Name English
PROBENECID COMPONENT OF PROBEN-C
Common Name English
NSC-18786
Code English
PROBENECID [WHO-IP]
Common Name English
Probenecid [WHO-DD]
Common Name English
PROBENECIDUM [WHO-IP LATIN]
Common Name English
PROBENECID [EP IMPURITY]
Common Name English
PROBEN-C COMPONENT PROBENECID
Common Name English
COL-PROBENECID COMPONENT PROBENECID
Common Name English
COLBENEMID COMPONENT PROBENECID
Common Name English
PROBALAN
Brand Name English
Classification Tree Code System Code
NCI_THESAURUS C921
Created by admin on Wed Jul 05 22:51:50 UTC 2023 , Edited by admin on Wed Jul 05 22:51:50 UTC 2023
LIVERTOX NBK548599
Created by admin on Wed Jul 05 22:51:50 UTC 2023 , Edited by admin on Wed Jul 05 22:51:50 UTC 2023
WHO-ATC M04AB01
Created by admin on Wed Jul 05 22:51:50 UTC 2023 , Edited by admin on Wed Jul 05 22:51:50 UTC 2023
WHO-VATC QM04AB01
Created by admin on Wed Jul 05 22:51:50 UTC 2023 , Edited by admin on Wed Jul 05 22:51:50 UTC 2023
Code System Code Type Description
DAILYMED
PO572Z7917
Created by admin on Wed Jul 05 22:51:50 UTC 2023 , Edited by admin on Wed Jul 05 22:51:50 UTC 2023
PRIMARY
IUPHAR
4357
Created by admin on Wed Jul 05 22:51:50 UTC 2023 , Edited by admin on Wed Jul 05 22:51:50 UTC 2023
PRIMARY
LACTMED
Probenecid
Created by admin on Wed Jul 05 22:51:50 UTC 2023 , Edited by admin on Wed Jul 05 22:51:50 UTC 2023
PRIMARY
HSDB
3387
Created by admin on Wed Jul 05 22:51:50 UTC 2023 , Edited by admin on Wed Jul 05 22:51:50 UTC 2023
PRIMARY
MERCK INDEX
M9142
Created by admin on Wed Jul 05 22:51:50 UTC 2023 , Edited by admin on Wed Jul 05 22:51:50 UTC 2023
PRIMARY Merck Index
EVMPD
SUB10053MIG
Created by admin on Wed Jul 05 22:51:50 UTC 2023 , Edited by admin on Wed Jul 05 22:51:50 UTC 2023
PRIMARY
ChEMBL
CHEMBL897
Created by admin on Wed Jul 05 22:51:50 UTC 2023 , Edited by admin on Wed Jul 05 22:51:50 UTC 2023
PRIMARY
EPA CompTox
DTXSID9021188
Created by admin on Wed Jul 05 22:51:50 UTC 2023 , Edited by admin on Wed Jul 05 22:51:50 UTC 2023
PRIMARY
WIKIPEDIA
Probenecid
Created by admin on Wed Jul 05 22:51:50 UTC 2023 , Edited by admin on Wed Jul 05 22:51:50 UTC 2023
PRIMARY
CAS
57-66-9
Created by admin on Wed Jul 05 22:51:50 UTC 2023 , Edited by admin on Wed Jul 05 22:51:50 UTC 2023
PRIMARY
RS_ITEM_NUM
1563003
Created by admin on Wed Jul 05 22:51:50 UTC 2023 , Edited by admin on Wed Jul 05 22:51:50 UTC 2023
PRIMARY
DRUG CENTRAL
2268
Created by admin on Wed Jul 05 22:51:50 UTC 2023 , Edited by admin on Wed Jul 05 22:51:50 UTC 2023
PRIMARY
MESH
D011339
Created by admin on Wed Jul 05 22:51:50 UTC 2023 , Edited by admin on Wed Jul 05 22:51:50 UTC 2023
PRIMARY
NSC
18786
Created by admin on Wed Jul 05 22:51:50 UTC 2023 , Edited by admin on Wed Jul 05 22:51:50 UTC 2023
PRIMARY
RXCUI
8698
Created by admin on Wed Jul 05 22:51:50 UTC 2023 , Edited by admin on Wed Jul 05 22:51:50 UTC 2023
PRIMARY RxNorm
SMS_ID
100000081091
Created by admin on Wed Jul 05 22:51:50 UTC 2023 , Edited by admin on Wed Jul 05 22:51:50 UTC 2023
PRIMARY
WHO INTERNATIONAL PHARMACOPEIA
PROBENECID
Created by admin on Wed Jul 05 22:51:50 UTC 2023 , Edited by admin on Wed Jul 05 22:51:50 UTC 2023
PRIMARY Description: A white or almost white, crystalline powder; odourless. Solubility: Practically insoluble in water; soluble in 25 parts of ethanol (~750 g/l) TS and in 12 parts of acetone R; soluble in dilutesolutions of alkali hydroxides. Category: Antigout drug. Storage: Probenecid should be kept in a well-closed container. Definition: Probenecid contains not less than 98.0% and not more than 101.0% of C13H19NO4S, calculated with reference to thedried substance.
FDA UNII
PO572Z7917
Created by admin on Wed Jul 05 22:51:50 UTC 2023 , Edited by admin on Wed Jul 05 22:51:50 UTC 2023
PRIMARY
CHEBI
8426
Created by admin on Wed Jul 05 22:51:50 UTC 2023 , Edited by admin on Wed Jul 05 22:51:50 UTC 2023
PRIMARY
INN
563
Created by admin on Wed Jul 05 22:51:50 UTC 2023 , Edited by admin on Wed Jul 05 22:51:50 UTC 2023
PRIMARY
DRUG BANK
DB01032
Created by admin on Wed Jul 05 22:51:50 UTC 2023 , Edited by admin on Wed Jul 05 22:51:50 UTC 2023
PRIMARY
NCI_THESAURUS
C772
Created by admin on Wed Jul 05 22:51:50 UTC 2023 , Edited by admin on Wed Jul 05 22:51:50 UTC 2023
PRIMARY
ECHA (EC/EINECS)
200-344-3
Created by admin on Wed Jul 05 22:51:50 UTC 2023 , Edited by admin on Wed Jul 05 22:51:50 UTC 2023
PRIMARY
PUBCHEM
4911
Created by admin on Wed Jul 05 22:51:50 UTC 2023 , Edited by admin on Wed Jul 05 22:51:50 UTC 2023
PRIMARY
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