Activity of sparftoxacin against<i>Mycobacterium leprae</i>inoculated into footpads of nude mice

Gidoh, Masaichi; Tsutsumi, Sadae

doi:10.5935/0305-7518.19920014

Cited by 6 publications

(3 citation statements)

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“…Sparfloxacin (AT-4140) was found to be the most active clinically relevant quinolone; its in vitro activity surpassed those of both pefloxacin and ofloxacin. Comparative studies (versus ofloxacin) in both nude mice (10,20) and healthy immune-competent mice (6,9) confirmed the in vitro observations. Considering its favorable plasma half-life of 17 h (13) and efficacy against other intracellular infections, sparfloxacin was chosen for a clinical trial in the treatment of patients with leprosy.…”

supporting

confidence: 55%

Clinical trial of sparfloxacin for lepromatous leprosy

Chan

Garcia-Ignacio

Chavez

et al. 1994

Antimicrob Agents Chemother

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Nine previously untreated patients with lepromatous leprosy were treated with 200 mg of sparfloxacin daily for 12 weeks to determine whether this drug is bactericidal for Mycobacterium leprae in humans. The efficacy of therapy was monitored both clinically and by measuring changes in morphological index, mouse footpad infectivity, and the radiorespirometric activity of M. leprae organisms obtained from serial biopsy specimens and also by determining titers of phenolic glycolipid-I in serum. Most patients showed clinical improvement within 2 weeks of treatment; this was accompanied by significant reductions in the morphological index, mouse footpad infectivity, and bacillary radiorespirometric activity. After 4 weeks of treatment, all patients had a morphological index of zero and specimens from most patients were noninfectious for mice, while the median decrease in radiorespirometric activity was >99%v. Overall results by the rapid radiorespirometric assay paralleled those of the mouse footpad and morphological index assays. Sparfloxacin given at 200 mg once daily appears to be rapidly bactericidal in humans, with activity similar to that observed in a previous clinical trial with 400 mg of ofloxacin.Among the fluoroquinolones, only ofloxacin and pefloxacin have been subjected to clinical trials in patients with leprosy (11), and both have displayed potent bactericidal activity. Sparfloxacin is a new fluoroquinolone with superior activity against most gram-positive bacteria (14) and Mycobacterium tuberculosis (16). The recent development of radiorespirometric assays for rapidly assessing the drug susceptibility of Mycobacterium leprae in vitro (5) made possible a comparative study of 20 fluoroquinolones (7). Sparfloxacin (AT-4140) was found to be the most active clinically relevant quinolone; its in vitro activity surpassed those of both pefloxacin and ofloxacin. Comparative studies (versus ofloxacin) in both nude mice (10, 20) and healthy immune-competent mice (6, 9) confirmed the in vitro observations. Considering its favorable plasma half-life of 17 h (13) and efficacy against other intracellular infections, sparfloxacin was chosen for a clinical trial in the treatment of patients with leprosy.A dosage of 200 mg of sparfloxacin given once daily was chosen on the basis of in vitro radiorespirometry (7), activity in the mouse footpad model (6), human pharmacokinetics (13), and the recommendation of the manufacturer.In addition to clinical response, morphological index (MI) and mouse footpad infectivity, this trial was monitored by measuring phenolic glycolipid-I (PGL-I) antigen levels in serum and radiorespirometric determination of the oxidation of palmitic acid by biopsy-derived M. leprae. Serum and biopsy specimens were collected just prior to the initiation of treatment and at 2-week intervals for 8 weeks. BI was determined from skin slit smears from at least six sites. MI (the percentage of solid-staining bacilli) was determined from slides prepared from homogenates of biopsy specimens. MATERIALS AND METHO...

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supporting

confidence: 55%

Clinical trial of sparfloxacin for lepromatous leprosy

Chan

Garcia-Ignacio

Chavez

et al. 1994

Antimicrob Agents Chemother

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“…Sparfloxacin, a potent inhibitor of bacterial DNA gyrase, is bactericidal at or near the minimum inhibitory concentration [1]. Sparfloxacin is effective against Gram-positive and Gram-negative bacteria and is more active against some micro-organisms, including staphylococci and mycobacteria, in vitro than other quinolones [2]. It is used in the treatment of community-acquired pneumonia and acute bacterial exacerbations of chronic bronchitis in adult patients [3,4].…”

Section: Introductionmentioning

confidence: 99%

Improvement and validation of an HPLC method for examining the effects of the MDR1 gene polymorphism on sparfloxacin pharmacokinetics

Cho

Park

Lee

2006

Journal of Chromatography B

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“…Sparfloxacin has demonstrated better activity in the clinical trials than other quinolones [1] against a broad range of gram-positive, gram-negative [2] and atypical pathogens. These organisms cause Sci Pharm.…”

Section: Introductionmentioning

confidence: 99%

Isolation and Characterization of an Impurity Obtained During the Synthesis of the Antibiotic Drug Sparfloxacin

Munigela

2009

Sci. Pharm.

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During the synthesis of Sparfloxacin, a fluoroquinolone antibiotic drug, an unknown impurity (SF5-IMP) was identified in the fifth stage of the synthetic process. The impurity has been isolated from the mother liquor of intermediate SF5. The mother liquor was concentrated to dryness added dichloromethane and stirred for 1 h and filtered to generate SF5-IMP and the molecular structure was elucidated as 7-amino-1-cyclopropyl-5,6,8-trifluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid by 19 F NMR and single crystal X-ray diffraction studies. The structural features of SF5-IMP and SF5 have been discussed here.

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Activity of sparftoxacin againstMycobacterium lepraeinoculated into footpads of nude mice

Cited by 6 publications

References 1 publication

Clinical trial of sparfloxacin for lepromatous leprosy

Clinical trial of sparfloxacin for lepromatous leprosy

Improvement and validation of an HPLC method for examining the effects of the MDR1 gene polymorphism on sparfloxacin pharmacokinetics

Isolation and Characterization of an Impurity Obtained During the Synthesis of the Antibiotic Drug Sparfloxacin

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