Open-label crossover study to determine pharmacokinetics and penetration of two dose regimens of levofloxacin into inflammatory fluid. Antimicrob. Agents. Chemother

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 mg/ml were attained 1.1 and 1.2 h after the 12- and 24-h regimens, respectively. Mean peak concentrations in inflammatory fluid of 6.8 and 4.3 mg/ml were attained at 2.3 and 3.7 h, respectively. The average steady-state concentrations were 5.0 and 2.2 mg/ml in plasma and 4.7 and 2.3 mg/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. Levofloxacin is an oral quinolone, the levo isomer of ofloxa-cin. In vitro studies suggest that it is approximately twice a