OPEN-LABEL CROSSOVER STUDY TO DETERMINE PHARMACOKINETICS AND PENETRATION OF 2 DOSE REGIMENS OF LEVOFLOXACIN INTO INFLAMMATORY FLUID

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 mu g/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 mu g/ml were attained at 2.3 and 3.7 h, respectively, The average steady-state concentrations were 5.0 and 2.2 mu g/ml in plasma and 4.7 and 2.3 mu g/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.