      Document 0194
 DOCN  DRG0194
 UNIQUE IDENTIFIER        DRG-0053
 NAME OF SUBSTANCE        Probenecid [USAN 1996]
 REGISTRY NUMBER          57-66-9
 STANDARD CHEMICAL NAME   4-((Dipropylamino)sulfonyl)benzoic acid [USAN
                          1996]
 SYNONYMS                 Benemid [USAN 1996]
 SYNONYMS                 Probecid [Merck Index 1989]
 SYNONYMS                 Proben [Merck Index 1989]
 SYNONYMS                 p-(Dipropylsulfamoyl)benzoic acid [Merck
                          Index 1989]
 SYNONYMS                 ColBenemid (component of) [USAN 1996]
 SYNONYMS                 Poly-PRB (component of) [USAN 1993]
 SYNONYMS                 Parabenem [USP DI 1989]
 SYNONYMS                 Probalan [USP DI 1995]
 SYNONYMS                 Benuryl [USP DI 1995]
 PROTOCOL ID NUMBERS      NIAID ACTG 027
 PROTOCOL ID NUMBERS      NIAID ACTG 107
 PROTOCOL ID NUMBERS      FDA 216A
 PROTOCOL ID NUMBERS      FDA 216B
 PROTOCOL ID NUMBERS      NIAID ACTG 281
 SECONDARY SOURCE ID      DRG
 PHARMACOLOGICAL ACTION   MODE OF ACTION: It inhibits the tubular
                          reabsorption of urate thereby increasing
                          urinary excretion of uric acid and decreasing
                          serum urate levels. Effective uricosuria
                          reduces the miscible urate pool, retards
                          urate deposition, and promotes resorption of
                          of urate deposits. Probenecid absorption is
                          rapid and complete, reaching peak
                          concentrations 2-4 hours after a 1 g dose.
                          Half-life is dose dependent and is 3 to 8
                          hours after a 500 mg dose and 6 to 12 hours
                          after larger doses. Protein binding is
                          75-95%. The drug is metabolized in the liver
                          and metabolites are excreted in the urine. An
                          alkaline urine increases excretion rate but
                          does not affect uricosuric activity. about
                          5-10% of the dose is excreted unchanged
                          within 24-48 hours. [PDR 1995; USP DI 1995]
 DISEASES STUDIED/TREATED Possible use in reducing the glucuronidation
                          of zidovudine (azidothymidine (AZT)), thereby
                          reducing the amount of AZT needed [USP DI
                          1995]
 CLASSIFICATION CODE      Uricosuric [USAN 1996]
 CLASSIFICATION CODE      Renal tubular blocker [PDR 1995]
 OTHER MAJOR USES         Chronic gouty arthritis and hyperuricemia
                          [PDR 1993] Used as an adjuvant to therapy
                          with penicillins in antibiotic therapy [PDR
                          1995]
 SUBSTANCE INTERACTIONS   Clinically significant interactions occur
                          with nonsteroidal anti-inflammatory agents,
                          especially indomethacin and ketoprofen.
                          Plasma levels of these agents are increased
                          which may result in enhanced therapeutic
                          effects or increased toxicity. Antineoplastic
                          agents which increase serum urate
                          concentrations should not be given with
                          probenecid since uric acid nephropaty may
                          occur. Any drugs which increase serum urate
                          concentrations should be used with caution.
                          Nitrofurantoin renal excretion is inhibited
                          by probencid. The renal excretion of
                          cephalosporins, penicillins and other
                          anti-infectives is inhibited by probenecid.
                          Aspirin and other salicylates may interfere
                          with probenecid's uricosuric effect.
                          Zidovudine serum levels are increased and its
                          half-life prolonged by probenecid. [USP DI
                          1995]
 ADVERSE EFFECTS          May cause headache, dizziness, precipitation
                          of acute gouty arthritis, hepatic necrosis,
                          vomiting, nausea, anorexia, sore gums,
                          nephrotic syndrome, uric acid stones,
                          with/without hematuria, renal colic,
                          costovertebral pain, urinary frequency,
                          anaphylaxis, fever, urticaria, pruritus,
                          aplastic anemia, leukopenia, hemolytic
                          anemia, anemia, dermatitis, alopecia,
                          flushing. [PDR 1995]
 CONTRAINDICATIONS        Should not be given to people with a known
                          hypersensitivity to probenecid or to children
                          under 2 years of age. Probenecid is not
                          recommended for patients with known blood
                          dyscrasias, uric acid kidney stones, or
                          during an acute attack of gout. [PDR 1995]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: A sulfonamide derivative
                          uricosuric drug. [AHFS Drug Information 1995]
 CHEMICAL/PHYSICAL DATA   MOLECULAR FORMULA: C13H19NO4S [USAN 1996]
 CHEMICAL/PHYSICAL DATA   MOLECULAR WEIGHT: 285.36 [USAN 1996]
 CHEMICAL/PHYSICAL DATA   ELEMENTAL COMPOSITION: C54.72%; H6.71%;
                          N4.91%; O22.43%; S11.23% [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   MELTING POINT: 194-196 C [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   PHYSICAL COMMENT: Slightly bitter taste,
                          pleasant aftertaste [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   SOLUBILITY: Soluble in chloroform and in
                          dilute solutions of NaOH buffered to pH 7.4;
                          nearly insoluble in water [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   PHYSICAL DESCRIPTION: White or practically
                          white, practically odorless, fine,
                          crystalline powder. [AHFS Drug Information
                          1995]
 SUBSTANCE DELIVERY DATA  DOSAGE FORM: Yellow capsule-shaped,
                          film-coated tablets (0.5 g). [PDR 1995]
 SUBSTANCE DELIVERY DATA  MODE OF DELIVERY: Oral. [PDR 1995]
 SUBSTANCE DELIVERY DATA  STORAGE INSTRUCTIONS: Store between 15 C and
                          30 C in a well-closed container. [USP DI
                          1995]
 MANUFACTURERS            Merck Sharp & Dohme
 MANUFACTURERS            Bristol-Myers
 MANUFACTURERS            Squibb
 REFERENCES               Lalezari JP, Drew WL, Glutzer E, James C,
                          Miner D, Flaherty J, Fisher PE, Cundy K,
                          Hannigan J, Martin JC, et al.
                          (S)-1-[3-hydroxy-2-(phosphonylmethoxy)propyl]-
                          cytosine (cidofovir): results of a phase I/II
                          study of a novel antiviral nucleotide
                          analogue. J Infect Dis. 1995
                          Apr;171(4):788-96.
 REFERENCES               Gaines K, Wong R, Jung D, Cimoch P, Lavelle
                          J, Pollard R, Pharmacokinetic interactions
                          with oral ganciclovir: zidovudine,
                          didanosine, probenecid. Int Conf AIDS. 1994
                          Aug 7-12;1091):7 (abstract no. 004B).
 REFERENCES               Rolfs R, Gold M, Hackett K, Augenbraun M,
                          Brady W, Larsen S. Treatment of early
                          syphilis in HIV-infected and HIV-uninfected
                          patients--preliminary report of the syphilis
                          & HIV study group. Int Conf AIDS. 1993 Jun
                          6-11;9(1):391 (abstract no. PO-B11-1534).
 REFERENCES               Berrebi A, Dumas JC, Giroux M, Teixeira MG,
                          Clottes A, Houin G, Grandjean H. AZT
                          materno-fetal and feto-maternal transfer: an
                          ex-vivo study. Int Conf AIDS. 1991 Jun
                          16-21;7(2):104 (abstract no. W.A.1048).
 REFERENCES               Hedaya MA, Elmquist WF, Sawchuk RJ.
                          Probenecid inhibits the metabolic and renal
                          clearances of zidovudine (AZT) in human
                          volunteers. Pharm Res. 1990 Apr;7(4):411-7.
 REFERENCES               Hedaya MA. ZIDOVUDINE PHARMACOKINETICS AND
                          INTERACTION STUDIES WITH PROBENECID.  Diss
                          Abstr Int [B]. 1990;50(8):3422.
 REFERENCES               de Miranda P, Good SS, Yarchoan R, Thomas RV,
                          Blum MR, Myers CE, Broder S. Alteration of
                          zidovudine pharmacokinetics by probenecid in
                          patients with AIDS or AIDS-related complex.
                          Clin Pharmacol Ther. 1989 Nov;46(5):494-500.
 REFERENCES               Hedaya MA, Elmquist WF, Sawchuk RJ.
                          Probenecid inhibits the metabolic and renal
                          clearances of zidovudine in human volunteers.
                          Int Conf AIDS. 1989 jun 4-9;5:203 (abstract
                          no. W.B.O.4).
 REFERENCES               Kornhauser DM, Petty BG, Hendrix CW, Woods
                          AS, Nerhood LJ, Bartlett JG, Lietman PS.
                          Probenecid and zidovudine metabolism [see
                          comments]. Lancet. 1989 Aug 26;2(8661):473-5.
 ENTRY MONTH              8906
 LAST REVISION DATE       960401
 

SOURCE: National Library of Medicine, Bethesda, MD.  Distributed by AEGIS.
