      Document 0118
 DOCN  DRG0118
 UNIQUE IDENTIFIER        DRG-0129
 NAME OF SUBSTANCE        Levofloxacin [USAN 1996]
 REGISTRY NUMBER          100986-85-4
 STANDARD CHEMICAL NAME   (-)-(S)-9-Fluoro-2,3-dihydro-3-methyl-10-
                          (4-methyl-1-piperazinyl)-7-oxo-7H-pyrido(1,2,-
                          3-de) -1,4-benzoxazine-6-carboxylic acid
                          [USAN 1996]
 SYNONYMS                 Ofloxacin (Related Compound) [AmFAR Tx Dir
                          1995;7(4)]
 SYNONYMS                 L-Ofloxacin [AmFAR Tx Dir 1995;7(4)]
 PROTOCOL ID NUMBERS      FDA 105A/B
 PROTOCOL ID NUMBERS      NIAID ACTG 222
 PROTOCOL ID NUMBERS      NIAID ACTG 238
 PROTOCOL ID NUMBERS      NIAID DATRI 008
 SECONDARY SOURCE ID      RWJ-25213 [AmFAR Tx Dir 1995;7(4)]
 SECONDARY SOURCE ID      DR-3355 [The Extra Pharmacopoeia 1993]
 PHARMACOLOGICAL ACTION   Exact mechanism of anti-HIV activity is
                          unknown, but in vitro studies have shown that
                          some fluoroquinolones (ciprofloxacin,
                          norfloxacin, and ofloxacin) can inhibit HIV
                          reverse transcriptase. Levofloxacin has
                          exhibited activity against gram-positive and
                          gram-negative bacteria, chlamydia,
                          mycoplasma, legionella, and mycobacteria. It
                          has a half-life of 6-7 hours, with peak
                          concentrations reached in approximately 1.5
                          hours. In a series of in vitro experiments
                          levofloxacin was about two-fold (with a range
                          between equal and four-fold) more active than
                          ofloxacin. [AmFAR Tx Dir 1995;7(4)] [NIAID
                          ACTG 222] [NIAID DATRI 008]
 DISEASES STUDIED/TREATED Primary HIV infection [AmFAR Tx Dir
                          1995;7(4)] [NIAID DATRI 008]
 DISEASES STUDIED/TREATED Tuberculosis [AmFAR Tx Dir 1995;7(4)] [NIAID
                          DATRI 008]
 CLASSIFICATION CODE      Antimicrobial [AmFAR Tx Dir Fall, 1991]
 CLASSIFICATION CODE      Antiretroviral [AmFAR Tx Dir Fall, 1991]
 OTHER MAJOR USES         Approved by the FDA for treatment of lower
                          respiratory; skin and soft tissue; sexually
                          transmitted diseases (C. trachmotis and N.
                          gon orrhea) and urinary tract infections,
                          including prostatitis (ofloxacin) [PDR 1995]
 ADVERSE EFFECTS          Adverse effects include gastrointestinal
                          disturbance, nausea, insomnia, and headache.
                          [AmFAR Tx Dir 1995;7(4)]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: The fluoroquinolone
                          levofloxacin (L-ofloxacin) is the
                          antimicrobially active isomer of ofloxacin
                          [AmFAR Tx Dir 1995;7(4)] [NIAID DATRI 008]
                          [The Extra Pharmacopoeia 1993]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: Ofloxacin is a commercially
                          available fluoroquinoline composed of a
                          racemic mixture of the d- and l-enantiomers,
                          of which the l-enantiomer is the active form
                          [AmFAR Tx Dir 1995;7(4)] [NIAID DATRI 008]
                          [The Extra Pharmacopoeia 1993]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: Levofloxacin is an
                          investigational drug whose formulation
                          consists solely of the l-enantiomer [AmFAR Tx
                          Dir 1995;7(4)] [NIAID DATRI 008] [The Extra
                          Pharmacopoeia 1993]
 CHEMICAL/PHYSICAL DATA   MOLECULAR FORMULA: C18H20FN3O4 [USAN 1996]
 CHEMICAL/PHYSICAL DATA   MOLECULAR WEIGHT: 361.38 [USAN 1996]
 CHEMICAL/PHYSICAL DATA   MELTING POINT: 250-257 C (ofloxacin) [Merck
                          Index 1989]
 CHEMICAL/PHYSICAL DATA   ELEMENTAL COMPOSITION: C59.82%, H5.58%,
                          F5.26%, N11.63%, O17.71% (ofloxacin) [Merck
                          Index 1989]
 SUBSTANCE DELIVERY DATA  DOSAGE FORM: 400 mg vials; 200-400 mg tablets
                          (ofloxacin). [PDR 1995]
 SUBSTANCE DELIVERY DATA  MODE OF DELIVERY: Oral; intravenous
                          (ofloxacin). [PDR 1995]
 SUBSTANCE DELIVERY DATA  STORAGE: Store below 30 C (86 F). Avoid
                          excessive heat and protect from freezing and
                          light (ofloxacin). [PDR 1995]
 MANUFACTURERS            Ortho Pharmaceutical Corporation
 REFERENCES               Chow AT, Wong FA, Rogge MC, and Flor SC.
                          Pharmacokinetics of levofloxacin after 500 mg
                          BID and 500 mg QD oral doses to two different
                          groups of healthy volunteers. Abstract, 4th
                          International Symposium on New Quinolones
                          (Munich, Germany) August 1992.
 REFERENCES               Billaud E, Moinard D, Bourgeot V, Raffi F.
                          Mycobacterium haemophilum (MH) cutaneous
                          infection: a case in an AIDS patient. Int
                          Conf AIDS. 1992 Jul 19-24;8(3):56 (abstract
                          no. PuB 7043).
 REFERENCES               Nakamori Y, TsuboiE, Narui K, Nakatani T, and
                          Sugi H. Sputum penetration of levofloxacin
                          and its clinical efficacy in patietns with
                          chronic lower respiratory infections. Jpn J
                          Antibiot 1992;45:539-547.
 REFERENCES               Fu KP, Lafredo SC, Foleno B, Isaacson Dm,
                          Barrett JF, Tobia AJ, and Rosenthale ME. In
                          vitro and in vivo antibacterial activities of
                          levofloxacin (l-ofloxacin), an optically
                          active ofloxacin. Antimicrob Agents Chemother
                          1992;36:860-866.
 REFERENCES               Nozaki-Renard J, Iino T, Sato Y, Marumoto Y,
                          Ohta G, Furusawa M. Fluoroquinolones protect
                          the human lyumphocyte CEM cell line from
                          HIV-1-mediated cytotoxicity. Cell Struct
                          Funct. 1990 Oct;15(5):295-9.
 REFERENCES               Furusawa M, Renard J, Iino T, Sato Y,
                          Marumoto Y, Ohta G. A fluoroquinolone
                          (DR-3355) protects human lymphocyte cell
                          lines from HIV-1-mediated cytotoxicity. Int
                          Conf AIDS. 1990 Jun 20-23;6(1):176 (abstract
                          no. Th.A.227).
 ENTRY MONTH              9111
 LAST REVISION DATE       951213
 

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