      Document 0104
 DOCN  DRG0104
 UNIQUE IDENTIFIER        DRG-0143
 NAME OF SUBSTANCE        Sparfloxacin [USAN 1996]
 REGISTRY NUMBER          111542-93-9 [CHEMLINE]
 RELATED REGISTRY NUMBER  110871-86-8
 STANDARD CHEMICAL NAME   3-Quinolinecarboxylic acid,
                          5-amino-1-cyclopropyl-7-
                          (3,5-dimethyl-1-piperazinyl)
                          -6,8-difluoro-1,4-dyhydro-4-oxo - [USAN 1996]
 SYNONYMS                 AT-4140 [USAN 1996]
 SYNONYMS                 CI-978 [USAN 1996]
 SYNONYMS                 PD-131501 [MeSH]
 SYNONYMS                 5-Amino-1-cyclopropyl-7-
                          (cis-3,5-dimethyl-1-piperazinyl)-6,8-difluoro-
                          -1,4-dihydro-4-oxo-3-quinolinecarboxylic acid
                          [USAN 1996]
 PROTOCOL ID NUMBERS      NIAID 92 I-165
 SECONDARY SOURCE ID      DRG
 PHARMACOLOGICAL ACTION   MODE OF ACTION: Potent inhibitor of bacterial
                          DNA gyrase, an enzyme that regulates the
                          supercoiling, uncoiling, and spatial geometry
                          of bacterial DNA. Sparfloxacin has enhanced
                          bactericidal activity against gram-positive
                          organisms. Since Mycobacterium avium complex
                          (MAC) can bind to and invade intestinal
                          mucosal cells, this study examined whether
                          subinhibitory concentrations of antibiotics
                          which have anti-MAC activity in vitro affect
                          the interaction between MAC and HT-29
                          intestinal mucosal cells. MAC exposed to
                          sparfloxacin at 1 and 7 mcg/ml inhibited
                          binding by 77-93%. Such binding inhibition
                          may be one underlying mechanism for the
                          prophylactic effects of rifabutin and
                          quinolones (e.g., sparfloxacin) In human
                          monocyte-derived macrophages infected with
                          MAC, sparfloxacin exhibited better efficacy
                          than rifapentine, azithromycin or
                          temafloxacin. [Antimicro Agents Chemother
                          1991 Jul;35(7)] [NIAID 92 I-165] [Antimicro
                          Agents Chemother 1994 May;38(5)]
 DISEASES STUDIED/TREATED Being investigated for the treatment of
                          tuberculosis [Tuber Lung Dis 1992 Dec;73(6)]
 DISEASES STUDIED/TREATED Treatment of MAI (Mycobacterium
                          avium-intracellular) bacteremia in
                          HIV-infected individuals [NIAID 92 I-165]
 CLASSIFICATION CODE      Antibacterial [USAN 1996]
 OTHER MAJOR USES         Sparfloxacin is expected to be useful for
                          treatment of Chlamydia trachomatis infection
                          in humans [In Conf AIDS 1994 Aug 7-12;10(1)]
 SUBSTANCE INTERACTIONS   In vitro synergism studies showed that
                          sparfloxacin plus ethambutol plus rifamycin
                          were synergistic against 10 strains of
                          Mycobacterium avium complex [Antimicro Agents
                          Chemother 1994 Dec;34(12)]
 ADVERSE EFFECTS          Adverse effects include hypersensitivity to
                          sunlight and gastrointestinal distress.
                          [NIAID 92 I-165]
 CONTRAINDICATIONS        Contraindicated in individuals with prolonged
                          QT intervals on EKG. [NIAID 92 I-165]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: A synthetic, broad
                          spectrum, fluoroquinolone antibacterial agent
                          [NIAID 92 I-165]
 CHEMICAL/PHYSICAL DATA   MOLECULAR FORMULA: C19H22F2N4O3 [USAN 1996]
 CHEMICAL/PHYSICAL DATA   MOLECULAR WEIGHT: 392.42 [USAN 1996]
 SUBSTANCE DELIVERY DATA  DOSAGE FORM: 100 mg tablets. [NIAID 92 I-165]
 SUBSTANCE DELIVERY DATA  MODE OF DELIVERY: Oral. [NIAID 92 I-165]
 MANUFACTURERS            Warner-Lambert Parke-Davis
 REFERENCES               Dautzenberg B. Clinical trials in
                          Mycobacterium avium therapy: lessons to take
                          home. Res Microbiol. 1994
                          Mar-Apr;145(3):197-206.
 REFERENCES               Kennedy N, Gillespie SH. Treatment of
                          tuberculosis in HIV infection [letter;
                          comment]. Tuber Lung Dis. 1993
                          Oct;74(5):347-9.
 REFERENCES               Peloquin CA. Controversies in the management
                          of Mycobacterium avium complex infection in
                          AIDS patients. Ann Pharmacother. 1993
                          Jul-Aug;27(7-8):928-37.
 REFERENCES               Tomioka H. [Expectation of new
                          antituberculous drugs and targeting therapy
                          for treatment of mycobacterial infections].
                          Kekkaku 1993 Nov;68(11):723-30.
 REFERENCES               Grosset JH. Treatment of tuberculosis in HIV
                          infection [see comments]. Tuber Lung Dis 1992
                          Dec;73(6):378-83.
 REFERENCES               Barlow D, Dimian C, Band B, Phillips I.
                          Chlamydia and Ureaplasma--genital symptoms.
                          Int Conf AIDS. 1992 Jul 19-24;8(2):B173
                          (abstract no. PoB 3519).
 REFERENCES               Pialoux G, Dupont B, Chamaret S, Lecoeur H,
                          Levy C, Montagnier L. Pilot study of
                          sparfloxacine + antiretroviral drug in
                          systemic mycoplasma infection in AIDS
                          patients. Int Conf AIDS. 1991 Jun
                          16-21;7(2):226 (abstract no. W.B.2176).
 REFERENCES               Perronne C, Gikas A, Truffot C, Grosset J,
                          Vilde JL, Pocidalo JJ. Sparfloxacin activity
                          against mycobacterium avium complex (MAC)
                          multiplication within human macrophages. Int
                          Conf AIDS. 1991 Jun 16-21;7(2):104 (abstract
                          no. W.A.1051).
 REFERENCES               Yajko DM, Sanders CA, Nassos PS, Hadley WK.
                          In vitro susceptibility of Mycobacterium
                          avium complex to the new fluoroquinolone
                          sparfloxacin (CI-978; AT-4140) and comparison
                          with ciprofloxacin. Antimicrob Agents
                          Chemother. 1990 Dec;34(12):2442-4.
 ENTRY MONTH              9206
 LAST REVISION DATE       960405
 

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