Penetration of fleroxacin into body tissues and fluids.
Concentrations of fleroxacin in human body fluids and tissues were studied to obtain information about the efficacy of the drug at the site of infection and the ratio of fleroxacin concentrations in tissue or fluid versus those in plasma as a measure of the extent of penetration. Samples of body fluids and tissues were obtained at various intervals after oral administration, and fleroxacin concentrations were determined by high-performance liquid chromatography. After administration of the standard dose of 400 mg once daily, the maximal plasma concentrations were 5-7 mg/L at steady-state and the minimal concentrations were approximately 1 mg/L at the end of the dosing interval. In most biologic specimens, such as myometrium, fallopian tube, bile bladder wall, bone, tonsils, maxillary sinus mucosa, prostatic adenoma, sputum, inflammatory fluid, synovia, lymph, saliva, and tears, the levels of fleroxacin were similar to those in plasma. In bile, nasal secretions, seminal fluid, lung, bronchial mucosa, and ovaries, the drug concentrations were 2-3 times higher than those in plasma. Penetration of fleroxacin into fat, lens, bronchial secretions, sweat, and aqueous humor was limited, with drug levels reaching only 10-40% of the concomitant levels in plasma. The measured concentration ratios did not vary markedly with time, and the decline in drug concentrations in tissues and fluids was generally parallel to that in plasma. The breakpoint for susceptibility is 1 micrograms/mL. The susceptibility breakpoint was exceeded by the drug concentration in plasma for the entire dosing interval and was also reached or exceeded in most body tissues and fluids.
Weidekamm
E
E
Department of Clinical Research, F. Hoffmann-La Roche Ltd., Basel, Switzerland.
Portmann
R
R
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001826:Body Fluids / Q000378:metabolism*; D001842:Bone and Bones / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D005260:Female; D016576:Fleroxacin / Q000493:pharmacokinetics*; D005836:Genitalia, Female / Q000378:metabolism*; D006801:Humans; D008168:Lung / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D013582:Synovial Fluid / Q000378:metabolism; D014018:Tissue Distribution
D016576:Fleroxacin