title: Open-label crossover study to determine pharmacokinetics and penetration of two dose regimens of levofloxacin into inflammatory fluid.
abstract: Two levofloxacin administration regimens were used for six healthy male volunteers. They received either 500 mg of levofloxacin orally every 12 h for five doses or 500 mg every 24 h for three doses, and then 6 weeks later they received the other course. The concentrations of the drug in plasma, cantharidin-induced inflammatory fluid, and urine were measured with a microbiological assay following administration of the final dose. Mean peak concentrations in plasma of 9.3 and 6.6 micrograms/ml were attained 1.1 and 1.2 h after the 12- and 24-h regimens, respectively. Mean peak concentrations is inflammatory fluid of 6.8 and 4.3 micrograms/ml were attained at 2.3 and 3.7 h, respectively. The average steady-state concentrations were 5.0 and 2.2 micrograms/ml in plasma and 4.7 and 2.3 micrograms/ml in inflammatory fluid, respectively. The mean terminal elimination half-lives for plasma were 7.9 and 8.0 h for the two regimens, respectively, and the same values were noted for inflammatory fluid. The overall penetration into inflammatory fluid ranged from 88 to 101% with the 12-h regimen and 83 to 112% with the 24-h regimen. Mean urinary recoveries were 87 and 86% over the corresponding interval of the 12- and 24-h regimens, respectively. These results suggest that administration of levofloxacin once and twice daily should be efficacious for infections caused by the majority of pathogens.
authors.affiliation: Department of Medical Microbiology, City Hospital NHS Trust, Birmingham, United Kingdom.
authors.forename: J
authors.initials: J
authors.lastname: Child
authors.forename: D
authors.initials: D
authors.lastname: Mortiboy
authors.forename: J M
authors.initials: JM
authors.lastname: Andrews
authors.forename: A T
authors.initials: AT
authors.lastname: Chow
authors.forename: R
authors.initials: R
authors.lastname: Wise
mesh_terms: D000293:Adolescent; D000328:Adult; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002193:Cantharidin; D018592:Cross-Over Studies; D004334:Drug Administration Schedule; D005122:Exudates and Transudates / Q000378:metabolism; D006207:Half-Life; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism*; D064704:Levofloxacin; D008297:Male; D008875:Middle Aged; D015242:Ofloxacin / Q000008:administration & dosage / Q000493:pharmacokinetics*
chemical_list: D000890:Anti-Infective Agents; D064704:Levofloxacin; D015242:Ofloxacin; D002193:Cantharidin