プロベネシド

EYES: First check the victim for contact lenses and remove if present. Flush victim's eyes with water or normal saline solution for 20 to 30 minutes while simultaneously calling a hospital or poison control center. Do not put any ointments, oils, or medication in the victim's eyes without specific instructions from a physician. IMMEDIATELY transport the victim after flushing eyes to a hospital even if no symptoms (such as redness or irritation) develop.

SMALL SPILLS AND LEAKAGE: If a spill of this chemical occurs, FIRST REMOVE ALL SOURCES OF IGNITION, then you should dampen the solid spill material with acetone and transfer the dampened material to a suitable container. Use absorbent paper dampened with acetone to pick up any remaining material. Seal your contaminated clothing and the absorbent paper in a vapor-tight plastic bag for eventual disposal. Solvent wash all contaminated surfaces with acetone followed by washing with a soap and water solution. Do not reenter the contaminated area until the Safety Officer (or other responsible person) has verified that the area has been properly cleaned.

RECOMMENDED RESPIRATOR: Where the neat test chemical is weighed and diluted, wear a NIOSH-approved half face respirator equipped with an organic vapor/acid gas cartridge (specific for organic vapors, HCl, acid gas and SO2) with a dust/mist filter. (NTP, 1992)

PROBENECID INHIBITS RENAL TRANSPORT OF ... PANTOTHENIC ACID, IODOMETHAMATE & RELATED IODINATED ORG ACIDS, AMINOHIPPURIC ACID, 17-KETOSTEROIDS PHENOLSULFONPHTHALEIN & SULFOBROMOPHTHALEIN. DOSAGE OF THESE AGENTS ... SHOULD BE MODIFIED WHEN THEY ARE ADMIN WITH PROBENECID. ... /IT ALSO/ INCR RENAL EXCRETION OF OXIPURINOL ... .

CONCURRENT ADMIN OF CEPHALEXIN & PROBENECID RESULTS IN HIGHER & PROLONGED SERUM ANTIBIOTIC LEVELS. ... CONCURRENT THERAPY DOES NOT APPEAR TO HAVE ANY CLINICAL ADVANTAGE OVER INCR IN ANTIBIOTIC DOSE.

/IN ADDN TO CEPHALEXIN/ OTHER CEPHALOSPORIN ANALOGS WHOSE SERUM LEVELS ARE ENHANCED BY PROBENECID ARE CEFAZOLIN, CEPHACETRILE, CEPHALOGLYCIN, CEPHALORIDINE, CEPHALOTHIN & CEPHRADINE.

CONCURRENT ADMIN OF PROBENECID, PARTICULARLY IN HIGH DOSES, DECR RENAL CLEARANCE OF NITROFURANTOIN & INCR SERUM LEVEL. ... INTERACTION MAY LEAD TO NITROFURANTOIN-INDUCED TOXICITY (EG, POLYNEUROPATHIES) OR DECR NITROFURANTOIN EFFICACY AS URINARY TRACT ANTI-INFECTIVE AGENT.

For more Interactions (Complete) data for PROBENECID (55 total), please visit the HSDB record page.

There are no reports on the frequency of liver test abnormalities during probenecid therapy, but they are probably rare as the drug is largely secreted unchanged in the urine. A single case report of a severe hypersensitivity reaction from probenecid and rechallenge with a rapid and severe recurrence of jaundice was reported over 50 years ago. As is typical for hypersensitivity reactions, the onset was within days of starting probenecid and was accompanied by fever and rash.

The following link will take the user to the National Toxicology Program (NTP) Test Agent Search Results page, which tabulates all of the "Standard Toxicology & Carcinogenesis Studies", "Developmental Studies", and "Genetic Toxicity Studies" performed with this chemical. Clicking on the "Testing Status" link will take the user to the status (i.e., in review, in progress, in preparation, on test, completed, etc.) and results of all the studies that the NTP has done on this chemical. [http://ntp-apps.niehs.nih.gov/ntp_tox/index.cfm?fuseaction=ntpsearch.searchresults&searchterm=57-66-9]

HUGE OVERDOSAGE OF PROBENECID RESULTS IN STIMULATION OF CNS, CONVULSIONS, & DEATH FROM RESP FAILURE.

... /OCCASIONALLY/ PATIENTS MAY EXPERIENCE ANOREXIA, NAUSEA, VOMITING, URINARY FREQUENCY, HYPERSENSITIVITY REACTIONS, SORE GUMS, FLUSHING, DIZZINESS & ANEMIA. NEPHROTIC SYNDROME, HEPATIC NECROSIS & APLASTIC ANEMIA OCCUR RARELY.

The most frequent adverse effects include headache, anorexia, nausea, and vomiting. Other reported adverse effects include dizziness, flushing, sore gums, alopecia, urinary frequency, leukopenia, and anemia. Nephrotic syndrome, hepatic necrosis, and aplastic anemia occur rarely. Mild to moderately severe hemolytic anemia, which in some patients could be related to genetic deficiency of glucose-6-phosphate dehydrogenase, has also been reported.

Hypersensitivity reactions which may be characterized by dermatitis, pruritus, fever, sweating, hypotension, and anaphylactic reaction occur rarely. Most cases of severe allergic reactions and anaphylaxis have been reported to occur within several hours after administration in patients who had previously received the drug. If a hypersensitivity reaction occurs in patients receiving probenecid, the drug should be discontinued. If rash occurs during administration of penicillin with probenecid and the causative agent cannot be determined, discontinuance of both drugs may be necessary.

For more Human Toxicity Excerpts (Complete) data for PROBENECID (7 total), please visit the HSDB record page.

Probenecid

TR-395: Toxicology and Carcinogenesis Studies of Probenecid (CASRN 57-66-9) in F344/N Rats and B6C3F1 Mice (Gavage Studies) (1991 )

11/20/90

No Evidence

No Evidence

No Evidence

Drug Induced Liver Injury Rank (DILIrank 2.0)

Probenecid

Ambiguous-DILI-concern

6

Adverse reactions

DOI:10.1016/j.drudis.2016.02.015

... /STUDIES HAVE SHOWN THAT PROBENECID BLOCKS/ THE TRANSPORT SYSTEM FOR ELIMINATION OF 5-HYDROXYINDOLEACETIC ACID (5HIAA) FROM BRAIN IN RATS.

Probenecid was tested for mutagenicity in the Salmonella/microsome preincubation assay using the standard protocol approved by the National Toxicology Program. Probenecid was tested at doses of 0.033, 0.10, 0.33, 1.0, and 3.3 mg/plate in as many as 5 Salmonella typhimurium strains (TA1535, TA1537, TA97, TA98, and TA100) in the presence and absence of rat or hamster liver S-9. Probenecid was negative in these tests and the highest ineffective dose tested in any Salmonella typhimurium strain mg/plate.

... Under the conditions of these 2 yr gavage studies, there was no evidence of carcinogenic activity of probenecid for male or female F344/N rats receiving 100 or 400 mg/kg in corn oil. There was no evidence of carcinogenic activity of probenecid for male B6C3F1 mice given 100 or 400 mg/kg probenecid in corn oil. There was some evidence of carcinogenic activity of probenecid for female B6C3F1 mice based on an increased incidence of hepatocellular adenomas.

... Toxicology and carcinogenicity studies were conducted by administering probenecid (>99% pure) in corn oil by gavage to groups of F344/N rats and B6C3F1 mice of each sex ... 5 days/wk ... for ... 2 yr. ... Doses of 0, 100, and 400 mg/kg were used for the 2 yr studies in rats and mice. These doses were administered once daily, 5 days/wk for up to 103 wk to groups of 50 males or 50 females of each species. Under the conditions of these 2 yr gavage studies, there was no evidence of carcinogenic activity of probenecid for male or female F344/N rats receiving 100 or 400 mg/kg in corn oil. There was no evidence of carcinogenic activity of probenecid for male B6C3F1 mice given 100 or 400 mg/kg probenecid in corn oil. There was some evidence of carcinogenic activity of probenecid for female B6C3F1 mice based on an increased incidence of hepatocellular adenomas.

Manufacturers, packers, and distributors of drug and drug products for human use are responsible for complying with the labeling, certification, and usage requirements as prescribed by the Federal Food, Drug, and Cosmetic Act, as amended (secs 201-902, 52 Stat. 1040 et seq., as amended; 21 U.S.C. 321-392).

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl probenecid, approved on the basis of safety and effectiveness by FDA under sections 505 and 507 of the Federal Food, Drug, and Cosmetic Act.

MEDICATION

Use (kg; approx.) in Germany (2009): >250

(1976) 6.15X10+6 GRAMS (PRINCPL CUSTMS DISTS)

(1978) 9.09X10+6 GRAMS (PRINCPL CUSTMS DISTS)

(1976) PROBABLY GREATER THAN 9.08X10+5 GRAMS

(1978) PROBABLY GREATER THAN 9.08X10+5 GRAMS

REACTION OF TOLUENE WITH CHLOROSULFONIC ACID FOLLOWED BY HYDROLYSIS AND OXIDATION YIELDS P-CARBOXYBENZENESULFONICACID, THEN TREATMENT OF THIS ACID WITH CHLOROSULFONIC ACID AND CONDENSATION WITH DI-N-PROPYLAMINE

PREPARATION FROM P-CARBOXYBENZENESULFONYL CHLORIDE & DIPROPYLAMINE.

PROBENECID (BENEMID, PROBALAN) IS MARKETED AS ORAL TABLETS (500 MG).

Oral Tablets, 500 mg, Benemid (scored), MSD; Probalan, Lannett; Tablets, film coated 500 mg.

Oral For suspension, Ampicillin (trihydrate) 3.5 g (of ampicillin) with Probenecid 1 g, Amplicillin and Probenecid Oral Suspension, Biocraft; Polycillin-BRB, Bristol-Myers; Probampacin, Goldline. /Ampicillin (Trihydrate) and Probenecid/

Oral Tablets 500 mg Probenecid and Colchincine 0.5 mg, ColBENEMID (scored), MSD; Col-Probenecid, Danbury, Goldline, United Research; Proben-C Rugby. /Probencid and Colchicine/

Tablets, 500 mg