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

Pharmacokinetic Evaluation of Oral Levofloxacin in Human Immunodeficiency Virus-Infected Subjects Receiving Concomitant Antiretroviral Therapy

“…Our results for 24 HIV-infected patients indicated that the systemic exposure to levofloxacin, when combined with NFV or with EFV, is not different from that previously observed in this population, when patients were not receiving these two antiretroviral agents (2, 6), or in healthy volunteers (3)(4)(5)(6)12). The longer levofloxacin T max observed in our patients taking EFV (3.3 h), if compared with the NFV group (1.4 h) or with historical controls (range, 0.9 to 1.7 h), may be referable to the delayed gastric-emptying phenomenon observed in a recent study of animals receiving EFV (1).…”

“…The pharmacokinetics (PK) of levofloxacin following single and multiple oral and intravenous doses have been widely studied (3)(4)(5)12; M. L. Holland, S. C. Chien, M. L. Corrado, et al, 5th Int. Symp.…”

Pharmacodynamic Modeling of the Evolution of Levofloxacin Resistance in Staphylococcus aureus

“…The main features and general operation of the system and the method for preparing standardized inocula for the experiments have been described previously (4). Log-phase cultures (ϳ10 7 CFU/ml) were exposed to a series of monoexponential levofloxacin pharmacokinetic profiles for 96 h. Three simulations were designed to reproduce the concentration-time profiles of clinical levofloxacin doses of 750 mg, 500 mg, and 250 mg administered as intermittent 1-hour infusions every 24 h. The simulated central and peripheral compartment concentrations were intended to mimic the total levofloxacin concentrations observed in plasma and skin blister fluid, respectively, of adult patients with normal renal function (6)(7)(8)(9)). An additional experimental regimen (125 mg every 24 h) was simulated to produce levofloxacin concentrations below the MPCs of the study strains for the entire duration of the experiment.…”

Steady-State Plasma and Bronchopulmonary Concentrations of Intravenous Levofloxacin and Azithromycin in Healthy Adults

“…Several observations would suggest that intrapulmonary concentrations of both drugs would be higher in patients with clinical conditions of inflammation and/or infection than in healthy volunteers. First, levofloxacin and azithromycin achieve high concentrations in the inflammatory infection model of blister fluid (9,18). Azithromycin and fluoroquinolones have displayed extensive accumulation by phagocytes which may allow further drug delivery at sites of infections (6,37).…”