Human Pharmacokinetics and Safety Profile of Finafloxacin, a New Fluoroquinolone Antibiotic, in Healthy Volunteers

Patel, Heena; Andresen, Arne F.; Vente, Andreas; Heilmann, Hans-Dietrich; Stubbings, Will; Seiberling, Michael; López-Lázaro, Luis; Pokorny, Rolf; Labischinski, Harald

doi:10.1128/aac.00832-10

Cited by 27 publications

(31 citation statements)

References 7 publications

(5 reference statements)

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“…anaerobiosis [5], in artificial and human urine [2,6] and in artificial and cystic fibrosis sputum [7] and it is also active against biofilms of bacterial cells and other quiescent forms of growth [8]. In addition, finafloxacin has demonstrated an excellent, high-dose-enabling safety profile both in preclinical and clinical studies, showing no indications of the cardiac or other toxic effects observed for other members of its class [9].…”

Section: Introductionmentioning

confidence: 98%

Activity of the investigational fluoroquinolone finafloxacin and seven other antimicrobial agents against 114 obligately anaerobic bacteria

Genzel¹,

Stubbings²,

Stîngu³

et al. 2014

International Journal of Antimicrobial Agents

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Section: Introductionmentioning

confidence: 98%

Activity of the investigational fluoroquinolone finafloxacin and seven other antimicrobial agents against 114 obligately anaerobic bacteria

Genzel¹,

Stubbings²,

Stîngu³

et al. 2014

International Journal of Antimicrobial Agents

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“…Finafloxacin, an investigational fluoroquinolone suitable for intravenous and oral administration, is being developed as sequential therapy for bacterial infections, including the treatment of UTIs (9). This compound exhibits essential features required to successfully treat such infections: good activity against Gram-positive, Gram-negative, and anaerobic pathogens with a bactericidal mechanism of action (4); a high level of excretion in the urine (10,11); and increased potency at acidic pH (4,5). Fluoroquinolones inhibit the activity of bacterial type II topoisomerases, i.e., DNA gyrase and topoisomerase IV.…”

mentioning

confidence: 99%

Explorative Randomized Phase II Clinical Study of the Efficacy and Safety of Finafloxacin versus Ciprofloxacin for Treatment of Complicated Urinary Tract Infections

Wagenlehner

Nowicki

Bentley

et al. 2018

Antimicrob Agents Chemother

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The broad-spectrum C-8-cyano-fluoroquinolone finafloxacin displays enhanced activity under acidic conditions. This phase II clinical study compared the efficacies and safeties of finafloxacin and ciprofloxacin in patients with complicated urinary tract infection and/or pyelonephritis. A 5-day regimen with 800 mg finafloxacin once a day (q.d.) (FINA05) had results similar to those of a 10-day regimen with 800 mg finafloxacin q.d. (FINA10). Combined microbiological and clinical responses at the test-of-cure (TOC) visit were 70% for FINA05, 68% for FINA10, and 57% for a 10-day ciprofloxacin regimen (CIPRO10) in 193 patients (64 for FINA05, 68 for FINA10, and 61 for CIPRO10) of the microbiological intent-to-treat (mITT) population. Additionally, the clinical effects of ciprofloxacin on patients with an acidic urine pH (80% of patients) were reduced, whereas the effects of finafloxacin were unchanged. Finafloxacin was safe and well tolerated. Overall, 43.4% of the patients in the FINA05 group, 42.7% in the FINA10 group, and 54.2% in the CIPRO10 group experienced mostly mild and treatment-emergent but unrelated adverse events. A short-course regimen of 5 days of finafloxacin resulted in high eradication and improved clinical outcome rates compared to those for treatment with ciprofloxacin for 10 days. In contrast to those of ciprofloxacin, the clinical effects of finafloxacin were not reduced by acidic urine pH. Hospitalized adults were randomized 1:1:1 to finafloxacin treatment (800 mg q.d.) for either 5 or 10 days or to ciprofloxacin treatment (400 mg/500 mg b.i.d.) for 10 days with an optional switch from intravenous (i.v.) to oral administration at day 3. The primary endpoint was the combined microbiological and clinical response at the TOC visit in the microbiological intent-to-treat population. (This study has been registered at ClinicalTrials.gov under identifier NCT01928433.).

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“…The level of urinary excretion of finafloxacin is high (47), and its activity is impaired neither by an acidic pH nor by high concentrations of divalent cations, which prevail in UTIs (48–50). In contrast, the activities of expanded-spectrum fluoroquinolones are diminished under such growth conditions (48, 49).…”

Section: Introductionmentioning

confidence: 99%

Pharmacodynamics of Finafloxacin, Ciprofloxacin, and Levofloxacin in Serum and Urine against TEM- and SHV-Type Extended-Spectrum-β-Lactamase-Producing Enterobacteriaceae Isolates from Patients with Urinary Tract Infections

Dalhoff

Schubert

Vente

2017

Antimicrob Agents Chemother

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The pharmacodynamics of finafloxacin, ciprofloxacin, and levofloxacin against extended-spectrum-β-lactamase (ESBL)-producing Enterobacteriaceae isolates were compared. Since quinolones lose activity in acidic media, and particularly in urine, their activities were tested in parallel under conventional conditions and in acidic artificial urine. For this purpose, TEM- and SHV-type ESBL-producing Escherichia coli and Klebsiella pneumoniae strains and their wild-type counterparts were exposed in a modified Grasso model to simulated concentrations of drugs in serum and urine following oral doses of either finafloxacin at 800 mg once a day (q.d.), immediate-release ciprofloxacin at 500 mg twice a day (b.i.d.), extended-release ciprofloxacin at 1,000 mg q.d., or levofloxacin at 500 or 750 mg q.d. The concentrations of the drugs in urine were fitted by compartmental modeling. Bacteria were cultivated in Mueller-Hinton broth (MHB) at pH 7.2 or 5.8 or in artificial urine at pH 5.8. Bacteria were counted every 2 h until 10 h and at 24 h; the areas under the bacterial-count–versus–time curves were calculated. It was found that finafloxacin eliminated all strains within 2 h under all the conditions studied. At all doses studied, ciprofloxacin and levofloxacin were highly active against wild-type strains in MHB at pH 7.2 but lost activity in MHB, and particularly in urine, at pH 5.8. Viable counts of ESBL producers were reduced for 6 to 8 h by 3 log10 titers, but the bacteria regrew thereafter. Ciprofloxacin and levofloxacin were almost inactive against the SHV producer grown in artificial urine. We conclude that pharmacodynamic models using artificial urine may mirror the physiology of urinary tract infections more closely than those using conventional media. In contrast to ciprofloxacin and levofloxacin, finafloxacin gained activity in this model at an acidic pH, maintained activity in artificial urine, and was active against TEM and SHV producers.

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Human Pharmacokinetics and Safety Profile of Finafloxacin, a New Fluoroquinolone Antibiotic, in Healthy Volunteers

Cited by 27 publications

References 7 publications

Activity of the investigational fluoroquinolone finafloxacin and seven other antimicrobial agents against 114 obligately anaerobic bacteria

Activity of the investigational fluoroquinolone finafloxacin and seven other antimicrobial agents against 114 obligately anaerobic bacteria

Explorative Randomized Phase II Clinical Study of the Efficacy and Safety of Finafloxacin versus Ciprofloxacin for Treatment of Complicated Urinary Tract Infections

Pharmacodynamics of Finafloxacin, Ciprofloxacin, and Levofloxacin in Serum and Urine against TEM- and SHV-Type Extended-Spectrum-β-Lactamase-Producing Enterobacteriaceae Isolates from Patients with Urinary Tract Infections

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