      Document 0054
 DOCN  DRG0054
 UNIQUE IDENTIFIER        DRG-0193
 NAME OF SUBSTANCE        SC-49483 [NIAID ACTG 259]
 PROTOCOL ID NUMBERS      NIAID ACTG 259
 SECONDARY SOURCE ID      DRG
 PHARMACOLOGICAL ACTION   MODE OF DELIVERY: SC-49483 does not have any
                          inherent anti-HIV activity but is converted
                          to SC-48334 in the intestinal wall. SC-48334,
                          an alpha glucosidase I inhibitor, when used
                          with AZT does appear to suppress HIV-1 in
                          vitro. A major problem with SC-48334 is
                          diarrhea with associated weight loss, thus
                          SC-49483 was developed to avoid this problem.
                          The mean oral bioavailability of SC-48334
                          from single doses of the SC-49483 was
                          estimated to be about 30% relative to the
                          single oral dose of SC-48334. SC-49483 was
                          administered orally to rats and cynomolgus
                          monkeys for 4 weeks. At dosages that gave
                          clinically meaningful plasma SC-48334
                          concentrations (8-10 mcg/ml), no diarrhea or
                          clinically severe toxicity was observed.
                          [NIAID ACTG 259] [AmFAR Tx Dir 1995;7(4)]
 DISEASES STUDIED/TREATED Primary HIV infection [NIAID ACTG 259]
 CLASSIFICATION CODE      Antiretroviral [NIAID ACTG 259]
 ADVERSE EFFECTS          Mild adverse effects noted include headache,
                          rash, abdominal pain, diarrhea, flatulence,
                          nausea, vomiting, temperature elevation, and
                          dizziness. [NIAID ACTG 259]
 CHEMICAL/PHYSICAL DATA   MOLECULAR WEIGHT: 499.65 [NIAID ACTG 259]
 SUBSTANCE DELIVERY DATA  DOSAGE FORM: 1 g capsules. [NIAID ACTG 259]
 SUBSTANCE DELIVERY DATA  MODE OF DELIVERY: Oral. [NIAID ACTG 259]
 MANUFACTURERS            G D Searle & Company
 REFERENCES               Tierney M, Pottage J, Kessler H, Fischl M,
                          Richman D, Merigan T, Powderly W, Smith S,
                          Karim A, Sherman J, et al. The tolerability
                          and pharmacokinetics of
                          N-butyl-deoxynojirimycin in patients with
                          advanced HIV disease (ACTG 100). The AIDS
                          Clinical Trials Group (ACTG) of the National
                          Institute of Allergy and Infectious Diseases.
                          J Acquir Immune Defic Syndr Hum Retrovirol
                          1995 Dec 15;10(5):549-53.
 REFERENCES               Fischer PB, Collin M, Karlsson GB, James W,
                          Butters TD, Davis SJ, Gordon S, Dwek RA,
                          Platt FM. The alpha-glucosidase inhibitor
                          N-butyldeoxynojirimycin inhibits human
                          immunodeficiency virus entry at the level of
                          post-CD4 binding. J Virol 1995
                          Sep;69(9):5791-7.
 REFERENCES               Kiso M, Ando K, Inagaki H, Ishida H, Hasegawa
                          A. Synthetic and structural studies of
                          alpha-sialyl-(2-->6) and alpha-sialyl-(2-->3)
                          1-deoxynojirimycin derivatives potentially
                          useful for biomedical applications. Carbohydr
                          Res 1995 Aug 11;272(2):159-78.
 REFERENCES               Cook CS, Karabatsos PJ, Schoenhard GL, Karim
                          A. Species dependent esterase activities for
                          hydrolysis of an anti-HIV prodrug glycovir
                          and bioavailability of active SC-48334. Pharm
                          Res 1995 Aug;12(8):1158-64.
 REFERENCES               Fischl MA, Resnick L, Coombs R, Kremer AB,
                          Pottage JC Jr, Fass RJ, Fife KH, Powderly WG,
                          Collier AC, Aspinall RL, et al. The safety
                          and efficacy of combination
                          N-butyl-deoxynojirimycin (SC-48334) and
                          zidovudine in patients with HIV-1 infection
                          and 200-500 CD4 cells/mm3. J Acquir Immune
                          Defic Syndr. 1994 Feb;7(2):139-47.
 REFERENCES               Bryant M, Mueller R, Partis R, Stolzenbach J,
                          Wyand M, Tiemeier D, Marr J. Efficacy and
                          safety of alpha-glucosidase inhibitor prodrug
                          SC-49483 in rhesus monkeys infected with SIV.
                          Int Conf AIDS. 1993 Jun 6-11;9(1):27
                          (abstract no. WS-A11-2).
 REFERENCES               Bryant M, Mueller R, Smidt M, Tiemeier D,
                          Jacobs G, Platt F, Butters T, Karlsson N,
                          Houseman K, Marr J. Anti-HIV properties of
                          alpha-glucosidase inhibitor SC-48334, the
                          active component of prodrug SC-49483. Int
                          Conf AIDS. 1993 Jun 6-11;9(1):33 (abstract
                          no. WS-A17-6).
 ENTRY MONTH              9402
 LAST REVISION DATE       960417
 

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