      Document 0169
 DOCN  DRG0169
 UNIQUE IDENTIFIER        DRG-0078
 NAME OF SUBSTANCE        SCH 39304 [CHEMLINE]
 REGISTRY NUMBER          121650-83-7
 SYNONYMS                 Threo-2-(2,4-difluorophenyl)-3-methylsulfonyl-
                          -1-(1H-1,2,4-triazol-1-yl)butan-2-ol [MeSH]
 SYNONYMS                 SM-8668 [Drugs Fut 1994 Dec; 19(12)]
 SYNONYMS                 Genaconazole [Drugs Fut 1994 Dec; 19(12)]
 PROTOCOL ID NUMBERS      NIAID ACTG 125
 IND NUMBER               32,338
 SECONDARY SOURCE ID      Sch-39304 [Antimicrob Agents Chemother. 1992
                          Dec;36(12)]
 SECONDARY SOURCE ID      SM-8668 [MeSH]
 SECONDARY SOURCE ID      Sch 42427 [MeSH]
 SECONDARY SOURCE ID      Sch-42427 [MeSH]
 SECONDARY SOURCE ID      Sch 42426 [MeSH]
 SECONDARY SOURCE ID      Sch-42426 [MeSH]
 PHARMACOLOGICAL ACTION   MODE OF ACTION: SCH 39304 appears to
                          effectively penetrate into the cerebrospinal
                          fluid (CSF), expressing its activity against
                          Cryptococcus neoformans infection. SCH 39304
                          is slowly eliminated following oral
                          administration of 50-200 mg, having a plasma
                          half-life of about 60 hours which is dose
                          independent. About 75 percent of the drug is
                          eliminated unchanged in the urine, with
                          clearance kinetics being dose independent.
                          Dose proportionality has been observed in
                          plasma peak levels, the area under the plasma
                          level-time curve, and the amount of drug
                          excreted in the urine. Maximum drug plasma
                          levels at steady state were 2.45, 4.73, 8.36,
                          and 15.49 mcg/ml at doses of 25, 50, 100, and
                          200 mg, respectively. Animal studies indicate
                          that the drug effectively penetrates into the
                          CSF, achieving concentrations active against
                          many opportunistic fungi and sustaining drug
                          concentrations in the CSF for at least 24
                          hours. [NIAID ACTG 125]
 DISEASES STUDIED/TREATED Cryptococcal meningitis [NIAID ACTG 125]
 DISEASES STUDIED/TREATED Oropharyngeal candidiasis [Antimicrob Agents
                          Chemother 1992 Dec; 36(12)]
 CLASSIFICATION CODE      Antifungal [Antimicrob Agents Chemother 1992
                          Dec;36(12)]
 SUBSTANCE INTERACTIONS   Preliminary results of a drug interaction
                          study of the drug with Mylanta/cimetidine
                          indicate that the absorption of SCH 39304 is
                          not inhibited by these drugs. [NIAID ACTG
                          125]
 ADVERSE EFFECTS          May cause headaches, nausea, diarrhea and
                          rash in humans. Slight, not clinically
                          significant elevations in liver enzymes have
                          been reported. Animal toxicity studies in
                          rodents, dogs, and primates have been
                          conducted. [NIAID ACTG 125] [J Acquir Immune
                          Defic Syndr 1992;5(6)]
 CONTRAINDICATIONS        Contraindicated in patients who have a
                          history of hypersensitivity to imidazole or
                          azole compounds, and in pregnant or lactating
                          women. [NIAID ACTG 125]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: Triazole derivative [NIAID
                          ACTG 125]
 CHEMICAL/PHYSICAL DATA   PHYSICAL DESCRIPTION: Crystalline powder
                          [NIAID ACTG 125]
 SUBSTANCE DELIVERY DATA  DOSAGE FORM: Tablets (100 mg). [NIAID ACTG
                          125]
 SUBSTANCE DELIVERY DATA  MODE OF DELIVERY: Oral. [Antimicrob Agents
                          Chemother 1992 Dec;36(12)]
 SUBSTANCE DELIVERY DATA  STORAGE: Store at controlled room temperature
                          (15-30 degrees C). [NIAID ACTG 125]
 MANUFACTURERS            Schering-Plough
 REFERENCES               Hostetler JS, Catanzaro A, Stevens DA,
                          Graybill JR, Sharkey PK, Larsen RA, Tucker
                          RM, al-Haidary AD, Rinaldi MG, Cloud GA, et
                          al. Treatment of coccidioidomycosis with SCH
                          39304. J Med Vet Mycol. 1994;32(2):105-14.
 REFERENCES               Anaissie EJ, Kontoyiannis DP, Vartivarian S,
                          Kantarjian HM, O'Brien S, Giralt SA,
                          Andersson BS, Karl C, Champlin RE, Bodey GP.
                          Effectiveness of an oral triazole for
                          opportunistic mold infections in patients
                          with cancer: experience with SCH 39304. Clin
                          Infect Dis. 1993 Dec;17(6):1022-31.
 REFERENCES               Graybill JR. Treatment of coccidioidomycosis.
                          Curr Top Med Mycol. 1993;5:151-79.
 REFERENCES               Hardin TC, Sharkey PK, Lam YF, Wallace JE,
                          Rinaldi MG, Graybill JR. Pharmacokinetics of
                          SCH-39304 in human immunodeficiency
                          virus-infected patients following chronic
                          oral dosing. Antimicrob Agents Chemother.
                          1992 Dec;36(12):2790-3.
 REFERENCES               Lee BL, Padula AM, Tauber MG, Chambers HF,
                          Sande MA. Oral SCH 39304 as primary, salvage,
                          and maintenance therapy for cryptococcal
                          meningitis in AIDS. J Acquir Immune Defic
                          Syndr. 1992;5(6):600-4.
 REFERENCES               Anaissie E, Gokaslan A, Hachem R, Rubin R,
                          Griffin G, Robinson R, Sobel J, Bodey G.
                          Azole therapy for trichosporonosis: clinical
                          evaluation of eight patients, experimental
                          therapy for murine infection, and review.
                          Clin Infect Dis. 1992 Nov;15(5):781-7.
 REFERENCES               Perfect JR, Wright KA, Hobbs MM, Durack DT.
                          Treatment of experimental cryptococcal
                          meningitis and disseminated candidiasis with
                          SCH39304. Antimicrob Agents Chemother. 1989
                          Oct;33(10):1735-40.
 ENTRY MONTH              9001
 LAST REVISION DATE       951128
 

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