Chemical: Drug
probenecid

PharmGKB contains no dosing guidelines for this . To report known genotype-based dosing guidelines, or if you are interested in developing guidelines, click here.



PharmGKB contains no Clinical Variants that meet the highest level of criteria.

Disclaimer: The PharmGKB's clinical annotations reflect expert consensus based on clinical evidence and peer-reviewed literature available at the time they are written and are intended only to assist clinicians in decision-making and to identify questions for further research. New evidence may have emerged since the time an annotation was submitted to the PharmGKB. The annotations are limited in scope and are not applicable to interventions or diseases that are not specifically identified.

The annotations do not account for individual variations among patients, and cannot be considered inclusive of all proper methods of care or exclusive of other treatments. It remains the responsibility of the health-care provider to determine the best course of treatment for a patient. Adherence to any guideline is voluntary, with the ultimate determination regarding its application to be made solely by the clinician and the patient. PharmGKB assumes no responsibility for any injury or damage to persons or property arising out of or related to any use of the PharmGKB clinical annotations, or for any errors or omissions.

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The table below contains information about pharmacogenomic variants on PharmGKB. Please follow the link in the "Variant" column for more information about a particular variant. Each link in the "Variant" column leads to the corresponding PharmGKB Variant Page. The Variant Page contains summary data, including PharmGKB manually curated information about variant-drug pairs based on individual PubMed publications. The PMIDs for these PubMed publications can be found on the Variant Page.

The tags in the first column of the table indicate what type of information can be found on the corresponding Variant Page.

Links in the "Gene" column lead to PharmGKB Gene Pages.

List of all variant annotations for probenecid

Gene ? Variant?
(147)
Alternate Names ? Chemicals ? Alleles ?
(+ chr strand)
Function ? Amino Acid?
Translation
No VIP available No VIP available VA G6PD Canton, Taiwan-Hakka, Gifu-like, Agrigento-like N/A N/A N/A
No VIP available No Clinical Annotations available VA
rs1045642 NC_000007.13:g.87138645A>G, NC_000007.14:g.87509329A>G, NG_011513.1:g.208920T>C, NM_000927.4:c.3435T>C, NP_000918.2:p.Ile1145=, rs10239679, rs11568726, rs117328163, rs17210003, rs2229108, rs386513066, rs60023214, rs9690664
A > G
SNP
I1145I
Alleles, Functions, and Amino Acid Translations are all sourced from dbSNP 147

Overview

Generic Names
  • probenicid
Trade Names
  • Apurina
  • Benecid
  • Benemid
  • Benuryl
  • Col-Probenecid
  • Colbenemid
  • Polycillin-PRB
  • Probalan
  • Probampacin
  • Probecid
  • Proben
  • Proben-C
  • Probenecid Acid
  • Probenemid
  • Probexin
  • Prolongine
  • Synergid R
  • Tubophan
  • Uricosid
Brand Mixture Names

PharmGKB Accession Id

PA451106

Type(s):

Drug

Description

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.

Source: Drug Bank

Indication

For the reduction of serum uric acid concentrations in chronic gouty arthritis and tophaceous gout in patients with frequent disabling gout attacks. Has also been effectively used to promote uric acid excretion in hyperuricemia secondary to the administration of thiazide and related diuretics.

Source: Drug Bank

Other Vocabularies

Information pulled from DrugBank has not been reviewed by PharmGKB.

Pharmacology, Interactions, and Contraindications

Mechanism of Action

Probenecid inhibits the tubular reabsorption of urate, thus increasing the urinary excretion of uric acid and decreasing serum urate levels. Probenecid may also reduce plasma binding of urate and inhibit renal secretion of uric acid at subtherapeutic concentrations. The mechanism by which probenecid inhibits renal tubular transport is not known, but the drug may inhibit transport enzymes that require a source of high energy phosphate bonds and/or nonspecifically interfere with substrate access to protein receptor sites on the kidney tubules.

Source: Drug Bank

Pharmacology

Probenecid is a uricosuric and renal tubular blocking agent and is used in combination with colchicine to treat chronic gouty arthritis when complicated by frequent, recurrent acute attacks of gout. It inhibits the reabsorption of urate at the proximal convoluted tubule, 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. At the proximal and distal tubles, probenecid competitively inhibits the secretion of many weak organic acids including penicillins, most cephalosporins, and some other beta-lactam antibiotics. This results in an increase in the plasma concentrations of acidic drugs eliminated principally by renal secretion, but only a slight increase if the drug is eliminated mainly by filtration. Thus, the drug can be used for therapeutic advantages to increase concentrations of certain beta-lactam antibiotics in the treatment of gonorrhea, neurosyphilis, or pelvic inflammatory disease (PID).

Source: Drug Bank

Food Interaction

Take with food to reduce irritation.|Increase liquid intake, avoid alcohol.

Source: Drug Bank

Absorption, Distribution, Metabolism, Elimination & Toxicity

Protein Binding

75-95%

Source: Drug Bank

Half-Life

6-12 hours

Source: Drug Bank

Route of Elimination

Excreted principally in the urine as monoacyl glucuronide and unchanged drug. Alkalinization of urine increases renal probenecid excretion.

Source: Drug Bank

Chemical Properties

Chemical Formula

C13H19NO4S

Source: Drug Bank

Isomeric SMILES

CCCN(CCC)S(=O)(=O)c1ccc(cc1)C(=O)O

Source: OpenEye

Canonical SMILES

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

Source: Drug Bank

Average Molecular Weight

285.359

Source: Drug Bank

Monoisotopic Molecular Weight

285.103478791

Source: Drug Bank

SMILES

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

Source: Drug Bank

InChI String

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)

Source: Drug Bank

PharmGKB Curated Pathways

Pathways created internally by PharmGKB based primarily on literature evidence.

  1. Uricosurics Pathway, Pharmacodynamics
    A stylized diagram of a renal proximal tubule cell to show the role of uricosuric drugs in preventing reabsorption of uric acid in human kidney.

Genes that are associated with this drug in PharmGKB's database based on (1) variant annotations, (2) literature review, (3) pathways or (4) information automatically retrieved from DrugBank, depending on the "evidence" and "source" listed below.

Curated Information ?

Drug Targets

Gene Description
ABCC1 (source: Drug Bank )
ALB (source: Drug Bank )
PANX1 (source: Drug Bank )
SLC22A11 (source: Drug Bank )
SLC22A6 (source: Drug Bank )
SLC22A8 (source: Drug Bank )

Drug Interactions

Interaction Description
aspirin - probenecid The salicylate decreases the uricosuric effect of probenecid (source: Drug Bank )
aspirin - probenecid Acetylsalicylic acid decreases the uricosuric effect of probenecid. (source: Drug Bank )
cefaclor - probenecid Probenecid increases the antibiotic's level (source: Drug Bank )
cefadroxil - probenecid Probenecid increases the antibiotic's level (source: Drug Bank )
cefadroxil - probenecid Probenecid increases the antibiotic's level (source: Drug Bank )
cefepime - probenecid Probenecid increases the antibiotic's level (source: Drug Bank )
cefixime - probenecid Probenecid increases the antibiotic's level (source: Drug Bank )
cefotaxime - probenecid Probenecid increases the antibiotic's level (source: Drug Bank )
cefotaxime - probenecid Probenecid increases the antibiotic's level (source: Drug Bank )
cefotetan - probenecid Probenecid increases the antibiotic's level (source: Drug Bank )
cefoxitin - probenecid Probenecid increases the antibiotic's level (source: Drug Bank )
cefoxitin - probenecid Probenecid increases the antibiotic's level (source: Drug Bank )
cefprozil - probenecid Probenecid increases the antibiotic's level (source: Drug Bank )
cefuroxime - probenecid Probenecid increases the antibiotic's level (source: Drug Bank )
cefuroxime - probenecid Probenecid increases the antibiotic's level (source: Drug Bank )
cephalexin - probenecid Probenecid increases the antibiotic's level (source: Drug Bank )
cephalexin - probenecid Probenecid increases the antibiotic's level (source: Drug Bank )
diflunisal - probenecid Probenecid increases toxicity of diflunisal (source: Drug Bank )
diflunisal - probenecid Probenecid increases toxicity of diflunisal (source: Drug Bank )
ganciclovir - probenecid Probenecid increases the effect and toxicity of ganciclovir/valganciclovir (source: Drug Bank )
ganciclovir - probenecid Probenecid increases the effect and toxicity of ganciclovir/valganciclovir (source: Drug Bank )
indomethacin - probenecid Probenecid increases the effect/toxicity of indomethacin (source: Drug Bank )
indomethacin - probenecid Probenecid increases the effect/toxicity of indomethacin (source: Drug Bank )
ketorolac - probenecid Probenecid increases toxicity of ketorolac (source: Drug Bank )
ketorolac - probenecid Probenecid increases toxicity of ketorolac (source: Drug Bank )
loracarbef - probenecid Probenecid increases the antibiotic's level (source: Drug Bank )
methotrexate - probenecid Probenecid increases the effect and toxicity of methotrexate (source: Drug Bank )
methotrexate - probenecid Probenecid increases the effect and toxicity of methotrexate (source: Drug Bank )
probenecid - aspirin The salicylate decreases the uricosuric effect of probenecid (source: Drug Bank )
probenecid - cefaclor Probenecid increases the antibiotic's level (source: Drug Bank )
probenecid - cefadroxil Probenecid increases the antibiotic's level (source: Drug Bank )
probenecid - cefadroxil Probenecid increases the antibiotic's level (source: Drug Bank )
probenecid - cefalotin Probenecid increases the antibiotic's level (source: Drug Bank )
probenecid - cefamandole Probenecid increases the antibiotic's level (source: Drug Bank )
probenecid - cefamandole Probenecid increases the antibiotic's level (source: Drug Bank )
probenecid - cefazolin Probenecid increases the antibiotic's level (source: Drug Bank )
probenecid - cefazolin Probenecid increases the antibiotic's level (source: Drug Bank )
probenecid - cefepime Probenecid increases the antibiotic's level (source: Drug Bank )
probenecid - cefixime Probenecid increases the antibiotic's level (source: Drug Bank )
probenecid - cefmetazole Probenecid increases the antibiotic's level (source: Drug Bank )
probenecid - cefonicid Probenecid increases the antibiotic's level (source: Drug Bank )
probenecid - cefotaxime Probenecid increases the antibiotic's level (source: Drug Bank )
probenecid - cefotaxime Probenecid increases the antibiotic's level (source: Drug Bank )
probenecid - cefotetan Probenecid increases the antibiotic's level (source: Drug Bank )
probenecid - cefoxitin Probenecid increases the antibiotic's level (source: Drug Bank )
probenecid - cefoxitin Probenecid increases the antibiotic's level (source: Drug Bank )
probenecid - cefprozil Probenecid increases the antibiotic's level (source: Drug Bank )
probenecid - cefradine Probenecid increases the antibiotic's level (source: Drug Bank )
probenecid - cefradine Probenecid increases the antibiotic's level (source: Drug Bank )
probenecid - ceftizoxime Probenecid increases the antibiotic's level (source: Drug Bank )
probenecid - cefuroxime Probenecid increases the antibiotic's level (source: Drug Bank )
probenecid - cefuroxime Probenecid increases the antibiotic's level (source: Drug Bank )
probenecid - cephalexin Probenecid increases the antibiotic's level (source: Drug Bank )
probenecid - cephalexin Probenecid increases the antibiotic's level (source: Drug Bank )
probenecid - cephaloglycin Probenecid increases the antibiotic's level (source: Drug Bank )
probenecid - diflunisal Probenecid increases toxicity of diflunisal (source: Drug Bank )
probenecid - diflunisal Probenecid increases toxicity of diflunisal (source: Drug Bank )
probenecid - ganciclovir Probenecid increases the effect and toxicity of ganciclovir/valganciclovir (source: Drug Bank )
probenecid - ganciclovir Probenecid increases the effect and toxicity of ganciclovir/valganciclovir (source: Drug Bank )
probenecid - indomethacin Probenecid increases the effect/toxicity of indomethacin (source: Drug Bank )
probenecid - indomethacin Probenecid increases the effect/toxicity of indomethacin (source: Drug Bank )
probenecid - ketorolac Probenecid increases toxicity of ketorolac (source: Drug Bank )
probenecid - ketorolac Probenecid increases toxicity of ketorolac (source: Drug Bank )
probenecid - loracarbef Probenecid increases the antibiotic's level (source: Drug Bank )
probenecid - methotrexate Probenecid increases the effect and toxicity of methotrexate (source: Drug Bank )
probenecid - methotrexate Probenecid increases the effect and toxicity of methotrexate (source: Drug Bank )
probenecid - salicylate-magnesium The salicylate decreases the uricosuric effect of probenecid (source: Drug Bank )
probenecid - salicylate-sodium The salicylate decreases the uricosuric effect of probenecid (source: Drug Bank )
probenecid - salicylate-sodium The salicylate, salicylate-sodium, decreases the uricosuric effect of probenecid. (source: Drug Bank )
probenecid - salsalate The salicylate, salsalate, decreases the uricosuric effect of probenecid. (source: Drug Bank )
probenecid - trisalicylate-choline The salicylate, trisalicylate-choline, decreases the uricosuric effect of probenecid. (source: Drug Bank )
probenecid - valganciclovir Probenecid increases the effect and toxicity of ganciclovir/valganciclovir (source: Drug Bank )
probenecid - valganciclovir Probenecid increases the effect and toxicity of ganciclovir/valganciclovir (source: Drug Bank )
probenecid - zidovudine Rash, malaise, myalgia (source: Drug Bank )
probenecid - zidovudine Rash, malaise, myalgia (source: Drug Bank )
valganciclovir - probenecid Probenecid may decrease excretion of Valganciclovir. Monitor for increased serum concentration and toxicity of Valganciclovir. (source: Drug Bank )
valganciclovir - probenecid Probenecid may decrease excretion of Valganciclovir. Monitor for increased serum concentration and toxicity of Valganciclovir. (source: Drug Bank )

Curated Information ?

Relationships from National Drug File - Reference Terminology (NDF-RT)

May Treat
Contraindicated With

Publications related to probenecid: 16

No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
PharmGKB summary: uric acid-lowering drugs pathway, pharmacodynamics. Pharmacogenetics and genomics. 2014. McDonagh Ellen M, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Allopurinol for chronic gout. The Cochrane database of systematic reviews. 2014. Seth Rakhi, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Towards Quantitation of the Effects of Renal Impairment and Probenecid Inhibition on Kidney Uptake and Efflux Transporters, Using Physiologically Based Pharmacokinetic Modelling and Simulations. Clinical pharmacokinetics. 2013. Hsu Vicky, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
PharmGKB summary: very important pharmacogene information for cytochrome P450, family 2, subfamily C, polypeptide 19. Pharmacogenetics and genomics. 2011. Scott Stuart A, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Very important pharmacogene summary: ABCB1 (MDR1, P-glycoprotein). Pharmacogenetics and genomics. 2011. Hodges Laura M, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Medications and glucose-6-phosphate dehydrogenase deficiency: an evidence-based review. Drug safety : an international journal of medical toxicology and drug experience. 2010. Youngster Ilan, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Is there a place for drug combination strategies using clinical pharmacology attributes?--review of current trends in research. Current clinical pharmacology. 2009. Srinivas Nuggehally R. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Pharmacokinetics of high-dose oseltamivir in healthy volunteers. Antimicrobial agents and chemotherapy. 2009. Wattanagoon Y, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Lack of effect of P-glycoprotein inhibition on renal clearance of dicloxacillin in patients with cystic fibrosis. Pharmacotherapy. 2008. Beringer Paul M, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Structure, function and regulation of P-glycoprotein and its clinical relevance in drug disposition. Xenobiotica; the fate of foreign compounds in biological systems. 2008. Zhou S-F. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Glucose-6-phosphate dehydrogenase deficiency. Lancet. 2008. Cappellini M D, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Ezetimibe: a review of its metabolism, pharmacokinetics and drug interactions. Clinical pharmacokinetics. 2005. Kosoglou Teddy, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Characterization of methotrexate transport and its drug interactions with human organic anion transporters. The Journal of pharmacology and experimental therapeutics. 2002. Takeda Michio, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
The anti-influenza drug oseltamivir exhibits low potential to induce pharmacokinetic drug interactions via renal secretion-correlation of in vivo and in vitro studies. Drug metabolism and disposition: the biological fate of chemicals. 2002. Hill George, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Role of MRP1 in multidrug resistance in acute myeloid leukemia. Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 1999. Legrand O, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Drug-induced haemolysis in glucose-6-phosphate dehydrogenase deficiency. British medical journal. 1976. Chan T K, et al. PubMed

LinkOuts

Web Resource:
Wikipedia
National Drug Code Directory:
0378-0156-01
DrugBank:
DB01032
KEGG Compound:
C07372
KEGG Drug:
D00475
PubChem Compound:
4911
PubChem Substance:
46506554
9576
Drugs Product Database (DPD):
294926
ChemSpider:
4742
Therapeutic Targets Database:
DAP001292
FDA Drug Label at DailyMed:
11e8d542-e79f-4665-8b35-8aa194c55f33

Clinical Trials

These are trials that mention probenecid and are related to either pharmacogenetics or pharmacogenomics.

No trials loaded.

NURSA Datasets

provided by nursa.org

No NURSA datasets available.

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Sources for PharmGKB drug information: DrugBank, PubChem.