      Document 0129
 DOCN  DRG0129
 UNIQUE IDENTIFIER        DRG-0118
 NAME OF SUBSTANCE        Alvircept sudotox [USAN 1996]
 REGISTRY NUMBER          137487-62-8
 SYNONYMS                 Soluble CD4-Pseudomonas Exotoxin [NIAID 91
                          I-155]
 SYNONYMS                 SCD4(178)-PE40 [MeSH]
 SYNONYMS                 sCD4-PE40 [AmFAR Tx Dir 1993;6(4)]
 PROTOCOL ID NUMBERS      NIAID 91 I-155
 PROTOCOL ID NUMBERS      NIAID ACTG 201
 PROTOCOL ID NUMBERS      FDA 084A
 PROTOCOL ID NUMBERS      NEI 92 EI-169
 SECONDARY SOURCE ID      U-85855 [USAN 1996]
 PHARMACOLOGICAL ACTION   MODE OF ACTION: In vitro, CD4-PE40
                          selectively kills cells expressing gp120. It
                          is inactive against cells latently infected
                          with HIV and uninfected cells. Addition of
                          CD4-PE40 to chronically infected HIV
                          lymphocytes inhibited protein synthesis, an
                          indication that the cells were highly
                          sensitive to the hybrid toxin. CD4-PE40
                          (10nM) selectively kills chronically
                          HIV-infected monocyte/macrophages (U1 cell
                          line) and inhibits HIV-1 spread in primary
                          macrophage cultures. The size of the CD4-PE40
                          molecule (60 kD) may be too large to cross
                          the blood-brain barrier. Following an 80
                          mcg/m2 IV dose, peak serum concentrations of
                          65-130 ng/ml were reached. The drug's
                          half-life was 3.6 hours. The volume of
                          distribution approximated the volume of
                          plasma (1.5 L/m2) with a clearance rate of
                          0.2-0.3 L/h/m2. [AmFAR Tx Dir 1995;7(4)] [J
                          Infect Dis 1994 Nov;170(5)]
 DISEASES STUDIED/TREATED Primary HIV infection [AmFAR Tx Dir
                          1995;7(4)]
 CLASSIFICATION CODE      Immunomodulator [AmFAR Tx Dir 1993;6(4)]
 CLASSIFICATION CODE      Antiretroviral [Facts and Comparisons 1996]
 SUBSTANCE INTERACTIONS   A strong synergistic activity exists between
                          CD4(178)-PE40 and AZT in blocking HIV spread;
                          a similar synergistic antiviral activity
                          exists with ddI. [Int Conf AIDS 1990 Jun
                          20-23;6(1):(abstract no. Th.A.248)]
 ADVERSE EFFECTS          Fatigue and reversible hepatic toxicity have
                          been noted in patients receiving up to 160
                          micrograms/m2. [AmFAR Tx Dir 1995;7(4)] [J
                          Infect Dis 1994 Nov;170(5)]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: CD4-PE40 is a recombinant
                          protein that contains the HIV-binding region
                          of human CD4 linked to the active domains of
                          Pseudomonas aeruginosa exotoxin A [AmFAR Tx
                          Dir 1995;7(4)]
 CHEMICAL/PHYSICAL DATA   MOLECULAR FORMULA: C2600H4130N748O812S10
                          [USAN 1996]
 CHEMICAL/PHYSICAL DATA   MOLECULAR WEIGHT: 59,187 daltons [USAN 1996]
 SUBSTANCE DELIVERY DATA  MODE OF DELIVERY: Intravenous. [AmFAR Tx Dir
                          1995;7(4)] [J Infect Dis 1994 Oct;170(4)]
 SUBSTANCE DELIVERY DATA  DOSAGE FORM: IV Injection [J Infect Dis 1994
                          Oct;170(4)]
 MANUFACTURERS            The Upjohn Company
 REFERENCES               Davey RT Jr, Boenning CM, Herpin BR, Batts
                          DH, Metcalf JA, Wathen L, Cox SR, Polis MA,
                          Kovacs JA, Falloon J, et al. Use of
                          recombinant soluble CD4 Pseudomonas exotoxin,
                          a novel immunotoxin, for treatment of persons
                          infected with human immunodeficiency virus. J
                          Infect Dis. 1994 Nov;170(5):1180-8.
 REFERENCES               Ramachandran RV, Katzenstein DA, Wood R,
                          Batts DH, Merigan TC. Failure of short-term
                          CD4-PE40 infusions to reduce virus load in
                          human immunodeficiency virus-infected
                          persons. J Infect Dis. 1994
                          Oct;170(4):1009-13.
 REFERENCES               Alston B, Mitsuyasu R, Lertora J, Flexner C,
                          Timpone J, van der Horst C. Phase I study of
                          sCD4-PE40 in HIV infected persons: (ACTG
                          201). Int Conf AIDS. 1993 Jun 6-11;9(1):498
                          (abstract no. PO-B29-2178).
 REFERENCES               Davey RT Jr, Boenning CM, Herpin BR, Batts
                          DH, Metcalf JA, Wathen L. A phase I
                          multi-dose trial of CD4-Pseudomonas exotoxin
                          (sCD4-PE40) in HIV-1 infected individuals.
                          Int Conf AIDS. 1993 Jun 6-11;9(1):478
                          (abstract no. PO-B26-2060).
 REFERENCES               Kennedy PE, Moss B, Berger EA. Primary HIV-1
                          isolates refractory to neutralization by
                          soluble CD4 are potently inhibited by
                          CD4-Pseudomonas exotoxin. Virology. 1993
                          Jan;192(1):375-9.
 REFERENCES               Davey RT Jr, Boenning CM, Herpin BR, Batts
                          DH, Walker RE, Polis MA, Falloon J, Kovacs
                          JA, Masur H, Metcalf JA, et al. A phase I
                          study of recombinant CD4-Pseudomonas exotoxin
                          (CD4-PE40) in HIV-infected individuals. Int
                          Conf AIDS. 1992 Jul 19-24;8(1):Mo8 (abstract
                          no. MoB 0020).
 REFERENCES               Verhoef J, Gekker G, Erice A, Peterson PK,
                          Balfour HH. Quantitative assay for testing
                          susceptibility of HIV isolates to zidovudine
                          and sCD4 (178)-PE40. Eur J Clin Microbiol
                          Infect Dis. 1992 Aug;11(8):715-21.
 REFERENCES               Rubino KL, Tarpley WG, Nicholas JA. Effects
                          of a soluble CD4 and CD4-Pseudomonas exotoxin
                          A chimeric protein on human peripheral blood
                          lymphocytes: lymphocyte activation and
                          anti-HIV activity in vitro. Antiviral Res.
                          1991 Oct;16(3):267-79.
 REFERENCES               Pitts TW, Bohanon MJ, Leach MF, McQuade TJ,
                          Marschke CK, Merritt JA, Wierenga W, Nicholas
                          JA. Soluble CD4-PE40 is cytotoxic for a
                          transfected mammalian cell line stably
                          expressing the envelope protein of human
                          immunodeficiency virus (HIV-1), and
                          cytotoxicity is variably inhibited by the
                          sera of HIV-1-infected patients. AIDS Res Hum
                          Retroviruses. 1991 Sep;7(9):741-50.
 ENTRY MONTH              9108
 LAST REVISION DATE       960313
 

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