Basic information Anti-gout drug Indications Side effects Chemical Properties Uses Production methods Safety Related Supplier
Probenecid Chemical Properties
- Melting point:194-196°C
- Boiling point:438.0±47.0 °C(Predicted)
- Density 1.2483 (rough estimate)
- refractive index 1.6800 (estimate)
- storage temp. Store at RT
- form neat
- pka5.8(at 25℃)
- Water Solubility <0.1 g/100 mL at 20 ºC
- Merck 14,7754
- Stability:Stable, but may be light sensitive. Incompatible with strong oxidizing agents.
- CAS DataBase Reference57-66-9(CAS DataBase Reference)
- NIST Chemistry ReferenceP-(dipropylsulfamoyl) benzoic acid(57-66-9)
- EPA Substance Registry SystemProbenecid (57-66-9)
Probenecid Usage And Synthesis
- Anti-gout drugProbenecid is a chemically synthetic sulfa anti-gout drug, also known as oxybenzone sulfonamides, which has dual role of both promoting the excretion of uric acid excretion and inhibiting the excretion of penicillin. Clinically it is used for treating chronic gout and suppressing excretion of penicillin-type drugs in order to increase their clinical plasma concentration as an adjuvant drug of penicillin therapy. Its mechanism of action is inhibiting the re-absorption of renal tubular on uric acid, thus increasing uric acid excretion and further lowering plasma uric acid concentration for reducing the deposition of urate in tissues and prevent the crystallization of urate. This product can also promote the dissolution of the pre-formed urate, thereby reducing its damage on the joint. In addition, the product can also competitively inhibit the secretion of a weak organic acid (such as penicillin, cephalosporins) in the renal tubules, which can increase blood concentrations of these antibiotics and prolong their duration of action. This product is easy for oral administration with a plasma protein binding rate of 85% to 90%. Adults take 1 g orally each time with the plasma concentration reaches peak after 2~4 hour and with a half-life of being 6 to 12 hours. Probenecid is rapidly metabolized in the liver with the major metabolite being probenecid acetyl glucuronic acid. The main metabolite is excreted through the urine. This product has no anti-inflammatory and analgesic effect, and thus being invalid for treating acute gout. Acute toxicity test results: orally: LD50 of rats being 1600mg/kg. After the oral administration, the major adverse reactions are gastrointestinal reactions with others adverse reactions including dizziness, headache, facial flushing, urinary frequency, gingival swelling and pain, skin rash; there are also occasional allergic reactions. It is not suitable for being applied to patients of acute gout and with history of uric acid crystal deposition in kidney and ureter. Patients of peptic ulcer or blood abnormalities and pregnant women should take with caution. Patients of renal dysfunction are not allowed for using it.
- Indications1. For treating hyperuricemia with chronic gouty arthritis and tophi, take 2 times per day for adults with the dose of each time being 25 mg, increase the dose to 2 times per day after 1 week with 500 mg each time. Upon the administration, maintain the daily intake of water being at 2500mL to prevent the formation of kidney stones, simultaneously take alkaline urine drug if necessary. But make sure that: 1, the filtration rate of glomerular should be greater than 50~60mL/min; 2, no kidney stones or history of kidney stones; 3, non-acidic urine; 4, patients of non-taking salicylates; 5, have regular tests of blood and urine pH value, liver and kidney function as well as the uric acid levels in blood and urine; 6, adjust the dose according to the clinical and uric acid level and maintain for a long time with the minimum effective amount.
2. As an adjunct drug for antibiotic treatment; it can be combined together with different antibiotics such as penicillin, ampicillin, oxacillin, amoxicillin ortho chlorine, and nafcillin; Probenecid can be used for inhibiting the discharge of these antibiotics, increase their blood concentration and can maintain for a relative long time.
The above information is edited by the Chemicalbook of Dai Xiongfeng.
- Side effects1. Gastrointestinal reactions: main reactions are that a small number of patients have loss of appetite, nausea, vomiting, and abdominal discomfort.
2. Central nervous system reactions and allergic reactions: occasional headache, facial flushing, fever and some allergic reactions such as itchy skin, dermatitis.
3. Other serious toxicities: for very few patients, they have got bleeding, neutropenia, aplastic anemia, nephrotic syndrome, and liver necrosis. Probenecid belongs to sulfa drugs, so patients with hypersensitivity to sulfa drugs are not allowed for using. Pregnant women, patients of peptic ulcer, liver and kidney dysfunction should use with caution. In addition, patients should drink lots of water for the medication should drink lots of water and add appropriate amount of sodium carbonate for preventing urinary stones. During the medication, people should pay attention to checking the blood.
- Chemical PropertiesWhite crystalline powder. Its melting point is 194-196 °C. It is soluble in acetone, and slightly soluble in ethanol or chloroform, but almost insoluble in water. It is also soluble in dilute sodium hydroxide solution, but almost insoluble in dilute acid. It is odorless with a slightly bitter taste.
- UsesIt is a kind of anti-gout drug. The product is organic acid, strongly fat-soluble, self-discharge from tubular secretion, very easily to be absorbed back. Therefore, in the presence of probenecid, the transfer of some organic acids in the tubular body will be inhibited, reducing the excretion of other organic acids. Thereby, it is used to treat chronic gout with being safe and effective. It has no effects on acute gout pain and inflammation and can’t be applied to acute gout.
It is used for the treatment of gout, rheumatoid arthritis and other chronic diseases.
- Production methodsToluene sulfonamide is oxidized by sodium dichromate to generate carboxylic benzenesulfonamide; then use bromopropane for alkylation, the resulting sodium probenecid is further acidified by acetate to obtain probenecid.
- Chemical PropertiesWhite to Off-White Solid
- Usespharmaceutical intermediate
- UsesFor 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 administra
- UsesAn inhibitor of several ABC-transporters of the subfamily ABCC or MRP.
- UsesUricosuric drug.
- DefinitionChEBI: A sulfonamide in which the nitrogen of 4-sulfamoylbenzoic acid is substituted with two propyl groups.
- IndicationsWhen probenecid (ColBENEMID) is given in sufficient amounts, it will block the active reabsorption of uric acid in the proximal tubules following its glomerular filtration, thereby increasing the amount of urate eliminated. In contrast, low dosages of probenecid appear to compete preferentially with plasma uric acid for the proximal tubule anionic transport system and thereby block its access to this active secretory system. The uricosuric action of probenecid, however, is accounted for by the drug’s ability to inhibit the active reabsorption of filtered urate.
- brand nameBenemid (Merck); Probalan (Lannett).
- General DescriptionProbenecid (Benemid) is the most widely used uricosuricagent in the United States. It is selectively excreted into therenal tubules by OATS. It is extensively metabolized via Ndealkylationor ω-oxidation, followed by phase II conjugationinto the active metabolite, p-sulfamyl hippurate, whichexhibits a high affinity, similar to p-aminohippurate, forbinding to OATS, thereby preventing uric acid reabsorptionfrom the renal proximal tubules.
- General DescriptionOdorless white or almost white crystalline powder. Slightly bitter taste; pleasant aftertaste.
- Air & Water ReactionsInsoluble in water.
- Reactivity ProfileProbenecid may be light sensitive .
- Fire HazardFlash point data for Probenecid are not available. Probenecid is probably combustible.
- Mechanism of actionProbenecid is rapidly absorbed after oral administration, with peak plasma levels usually reached in 2 to 4 hours. Its half-life is somewhat variable (6–12 hours) because of both its extensive plasma protein binding and its active proximal tubular secretion. Since tubular backdiffusion is decreased at alkaline urinary pH ranges, probenecid excretion increases with increasing urinary pH. Probenecid is rapidly metabolized, with less than 5% of an administered dose being eliminated in 24 hours.The major metabolite is an acyl monoglucuronide.
- Clinical UseProbenecid is an effective and relatively safe agent
for controlling hyperuricemia and preventing tophi
deposition in tissues. Chronic administration will decrease
the incidence of acute gouty attacks as well as diminish
the complications usually associated with hyperuricemia,
such as renal damage and tophi deposition.
Probenecid is still used by some physicians to maintain high blood levels of penicillin, cephalosporin, acyclovir, and cyclosporine. It is not useful in treating acute attacks of gouty arthritis. If the total amount of uric acid excreted is greater than 800 mg/day, the urine should be alkalinized to prevent kidney stone formation and promote uric acid.
- Veterinary Drugs and TreatmentsAlthough there has been very limited clinical use or research on
probenecid in veterinary medicine, it can be useful in treating gout
(hyperuricemia), particularly in reptiles.
Probenecid’s effect in inhibiting renal tubular secretion of certain beta-lactam antibiotics and other weak organic acids is of interest for increasing serum concentrations, or reducing doses and dosing frequency of these drugs. This may allow greater efficacy (but also toxic effects) and reduce the cost or dosing frequency of expensive human drugs. Probenecid has a significantly long elimination halflife in dogs (about 18 hours), which may make it particularly useful in this species; however, at present there is little research supporting this use of probenecid in veterinary patients.
Probenecid Preparation Products And Raw materials
- Probenecid sodium AQUANTRAAL Sulfuryl chloride AKOS BBS-00000344 Probenecid-d14,Probenecid-d14 Acid 4-(3,5-DIMETHYL-PIPERIDINE-1-SULFONYL)-BENZOIC ACID 4-[(3-METHYLPIPERIDIN-1-YL)SULFONYL]BENZOIC ACID AKOS BBS-00000356 4-DIISOBUTYLSULFAMOYL-BENZOIC ACID 4-[BIS-(2-CYANO-ETHYL)-SULFAMOYL]-BENZOIC ACID 4-(AZEPANE-1-SULFONYL)-BENZOIC ACID Benzoic acid, 4-((dipentylamino)sulfonyl)- 4-(2,6-DIMETHYL-MORPHOLINE-4-SULFONYL)-BENZOIC ACID Probenecid Oxydipropyl dibenzoate 4-Aminobenzoic acid BENZOICACID 4-Dimethylaminobenzoic acid
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