      Document 0111
 DOCN  DRG0111
 UNIQUE IDENTIFIER        DRG-0136
 NAME OF SUBSTANCE        Sorivudine [USAN 1996]
 REGISTRY NUMBER          77181-69-2
 RELATED REGISTRY NUMBER  80434-16-8
 STANDARD CHEMICAL NAME   2,4(1H,3H)-Pyrimidinedione,
                          1-beta-D-arabinofuranosyl-5-(2-bromoethenyl)-
                          [USAN 1996]
 SYNONYMS                 BV ara-U [AmFAR Tx Dir 1993;6(4)]
 SYNONYMS                 BV-araU [Microbial Immunol 1991;35(2)]
 SYNONYMS                 1-beta-D-arabinofuranosyl-E-5-(2-bromovinyl)u-
                          racil [Antimicrob Agents Chemother 1990
                          May;34(5)]
 SYNONYMS                 SQ 32,756 [USAN 1996]
 SYNONYMS                 5-(2-bromovinyl)-1-beta-D-arabinofuranosylura-
                          cil [MeSH]
 SYNONYMS                 1-beta-D-arabinofuranosyl-5-(2-bromovinyl)ura-
                          cil [MeSH]
 SYNONYMS                 Bravavir [USAN 1996]
 SYNONYMS                 Brovavir [Antimicrob Agents Chemother 1990
                          May;34(5)]
 PROTOCOL ID NUMBERS      NIAID ACTG 169
 PROTOCOL ID NUMBERS      FDA 255A
 SECONDARY SOURCE ID      YN-72 [USAN 1996]
 PHARMACOLOGICAL ACTION   Brovavir is transported into viral-infected
                          cells and converted to monophosphate
                          analogues by virus-encoded thymidine kinase.
                          Requires a virus-encoded thymidylate kinase
                          to be converted to a diphosphate analogue.
                          Does not appear to be incorporated into
                          cellular DNA, but acts as an inhibitor of
                          virus-encoded DNA polymerase. Low toxic
                          potential for normal cells. In prior human
                          studies, mean serum elimination half-life was
                          5 hours. Pre-clinical toxicity profile
                          suggest that brovavir may be as well
                          tolerated as acyclovir. [AmFAR Tx Dir
                          1993;6(4)] [NIAID ACTG 169]
 DISEASES STUDIED/TREATED Active against HSV-1 and varicella-zoster
                          virus (VZV) [AmFAR Tx Dir 1993;6(4)]
 CLASSIFICATION CODE      Antiviral [USAN 1996]
 OTHER MAJOR USES         Herpesvirus infections [J Antimicrob
                          Chemother 1993 Suppl A;32]
 ADVERSE EFFECTS          In studies in Japan, no apparent side effects
                          were noted when HIV-negative subjects were
                          given oral doses up to 600 mg/d for 5 days.
                          [AmFAR Tx Dir 1993;6(4)]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: Antiviral nucleoside analog
                          [AmFAR Tx Dir 1993;6(4)]
 CHEMICAL/PHYSICAL DATA   MOLECULAR FORMULA: C11H13BrN2O6 [USAN 1996]
 CHEMICAL/PHYSICAL DATA   MOLECULAR WEIGHT: 349.14 [USAN 1996]
 SUBSTANCE DELIVERY DATA  DOSAGE FORM: 40 mg capsules. [NIAID ACTG 169]
 SUBSTANCE DELIVERY DATA  MODE OF DELIVERY: Oral; intravenous. [AmFAR
                          Tx Dir 1993;6(4)]
 MANUFACTURERS            Bristol-Myers Squibb Company
 REFERENCES               Olsen SJ, Saag M, Sommadossi JP, Hedden BC,
                          Raymond R, Stewart MB. Safety and
                          pharmacokinetic interaction of sorivudine
                          (BV-araU) and zidovudine. Program Abstr
                          Intersci Conf Antimicrob Agents Chemother.
                          1994 Oct 4-7;:82.
 REFERENCES               Boag F, Bodsworth NJ, Burdge D, Genereux M,
                          Barleffs JC, Evans B, Colebunders R, Modai J,
                          Thomas M, Marcoccia J, et al. The safety and
                          efficacy of sorivudine (BV-araU) for the
                          treatment of zoster in HIV-infected adults:
                          results of a multinational acyclovir
                          controlled trial. Annu Conf Australas Soc HIV
                          Med. 1994 Nov 3-6;6:166 (unnumbered
                          abstract).
 REFERENCES               Pinnolis MK, Foxworthy D, Kemp B. Treatment
                          of progressive outer retinal necrosis with
                          sorivudine. Am J Ophthalmol. 1995
                          Apr;119(4):516-7.
 REFERENCES               Talarico CL, Phelps WC, Biron KK. Analysis of
                          the thymidine kinase genes from
                          acyclovir-resistant mutants of
                          varicella-zoster virus isolated from patients
                          with AIDS. J Virol. 1993 Feb;67(2):1024-33.
 REFERENCES               Ijichi K, Ashida N, Varia S, Machida H.
                          Topical treatment with BV-araU of
                          immunosuppressed and immunocompetant shaved
                          mice cutaneously infected with herpes simplex
                          virus type 1. Antiviral Res 1993
                          May;21(1):47-57.
 REFERENCES               Machida H, Ijichi K, Takezawa J. Efficacy of
                          oral treatment with BV-araU against cutaneous
                          infection with herpes simplex type 1 in
                          shaved mice. Antiviral Res 1992
                          Feb;17(2):133-43.
 REFERENCES               Hiraoka A, Masaoka T, Nagai K, Horiuchi A,
                          Kanamaru A, Niimura M, Hamada T, Takahashi M.
                          Clinical effect of BV-araU on
                          varicella-zoster virus infection in
                          immunocompromised patients with
                          haematological malignancies. J Antimicrob
                          Chemother 1991 Mar;27(3):361-7.
 REFERENCES               Niimura M. A double-blind clinical study in
                          patients with herpes zoster to establish
                          YN-72 (Brovavir) dose. Adv Exp Med Biol
                          1990;278:267-75.
 REFERENCES               Machida H, Nishitani M. Drug susceptibilities
                          of isolates of varicella-zoster virus in a
                          clinical study of oral behavior. Microbiol
                          Immunol 1990;34(4):407-11.
 REFERENCES               Soike KF, Baskin G, Cantrell C, Gerone P.
                          Investigation of antiviral activity of
                          1-beta-D-arabinofuranosylthymine (ara-T) and
                          1-beta-D-arabinofuranosyl-E-5-(2-bromovinyl)u-
                          racil (BV-ara-U) in monkeys infected with
                          simian varicella virus. Antiviral Res
                          1984;4(5):245-257.
 ENTRY MONTH              9201
 LAST REVISION DATE       960514
 

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