Pharmacokinetics and tissue penetration of fleroxacin after single and multiple 400- and 800-mg-dosage regimens

To enhance the antimicrobial spectrum of the quinolones against anaerobic organisms and gram-positive bacteria, we investigated in two studies the parenteral combinations of ciprofloxacin (200 mg) and ofloxacin (200 mg) with metronidazole (500 mg) or clindamycin (600 mg) and the oral combinations of enoxacin (400 mg) and fleroxacin (400 mg) with metronidazole (400 mg), clindamycin (300 mg), or ornidazole (500 mg) (only with fleroxacin). The pharmacokinetics and serum bactericidal activities (SBAs) against 5 aerobic and 2 anaerobic species (total, 58 strains) were determined in two groups of 10 healthy volunteers by using a randomized crossover study design. The additions of metronidazole, clindamycin, and ornidazole did not affect the pharmacokinetics of the quinolones. The combination of clindamycin with ciprofloxacin, ofloxacin, and, to a lesser extent, fleroxacin resulted in an increase of the SBA against gram-positive strains (mean peak titers): Staphylococcus aureus, ciprofloxacin alone, 1:5.5; ciprofloxacin-clindamycin, 1:19.9; ofloxacin alone, 1:3.6; ofloxacin-clindamycin, 1:17.5; fleroxacin alone, 1:4.3; fleroxacin-clindamycin, 1:8.1; Streptococcus pneumoniae (fleroxacin and enoxacin were not tested), ciprofloxacin alone, 1:2.0; ciprofloxacin-clindamycin, 1:53; ofloxacin alone, 1:2.6; and ofloxacin-clindamycin, 1:49.2. The high SBA of quinolones against gram-negative bacteria was not affected by the combinations; however, relatively low activities against Pseudomonas aeruginosa were detected. In general, against anaerobic bacteria, low bactericidal activities were determined in both studies (mean peak titers ranged from 1:2

Section: Discussionsupporting

confidence: 82%

“…Thus, an oral once-a-day treatment seems to be possible (6,13,31,33,42). Enoxacin is available as an oral and parenteral drug characterized by a high bioavailability, a good tissue penetration after oral administration, and an antibacterial spectrum similar to that of fleroxacin (6).…”

mentioning

confidence: 99%

Pharmacokinetics and serum bactericidal activities of quinolones in combination with clindamycin, metronidazole, and ornidazole

Boeckh

Lode

Deppermann

et al. 1990

“…For fleroxacin, the corresponding values were 14.16 ± 3.01 and 1.21 ± 0.66 ,ug/ml. This peak concentration of fleroxacin in serum is similar to that observed in humans following multiple oral doses of 800 mg (11).…”

Section: Resultssupporting

confidence: 62%

Development of resistance to fleroxacin during therapy of experimental methicillin-susceptible Staphylococcus aureus endocarditis

Kaatz

Seo

Barriere

et al. 1991

“…Animal studies have suggested that there is excellent penetration of drug into most tissues (5, 18, 30-34, 41, 49, 53), but only limited information on tissue penetration of fleroxacin in humans is available (22,26,41,44,53). Initial clinical experience in the treatment of sexually transmitted diseases, urinary tract infection, skin and soft tissue infections, gastrointestinal infection, and even acute exacerbations of chronic bronchitis has been quite promising, with 74 to 100% bacteriological cure rates and a tolerability comparable to those for other drugs of this class (3,12,27,35,38,42,43,45,47).…”

mentioning

confidence: 99%

Pharmacokinetics of [18F]fleroxacin in healthy human subjects studied by using positron emission tomography

Fischman

Livni

Babich

et al. 1993

Positron emission tomography (PET) with [18Fjfleroxacin was used to study the pharmacokinetics of fleroxacin, a new broad-spectrum fluoroquinolone, in 12 healthy volunteers (9 men and 3 women). The subjects were infused with a standard therapeutic dose of fleroxacin (400 mg) supplemented with -20 mCi of[18F]fleroxacin. Serial PET images were made and blood samples were collected for 8 h, starting at the initiation of the infusion. The subjects were then treated with unlabeled drug for 3 days (400 mg/day). On the fifth day, infusion of radiolabeled drug, PET imaging, and blood collection were repeated. In most organs, there was rapid accumulation of radiolabeled drug, with stable levels achieved within 1 h after completion of the infusion.Especially high peak concentrations (in micrograms per gram) were achieved in the kidney (>34), liver (>25), lung (>20), myocardium (>19), and spleen (>18). Peak concentrations of drug more than two times the MIC for 90% of Enterobacteriaceae strains tested (>10-fold for most organisms) were achieved in all tissues except the brain and remained above this level for more than 6 to 8 h. The plateau concentrations in tissues (2 to 8 h, in micrograms per gram ± standard error of the mean) of drug were as follows: brain, 0.