Use of Pharmacodynamic End Points in the Evaluation of Gatifloxacin for the Treatment of Acute Maxillary Sinusitis

Abstract

The relationship between drug exposure and the time course of antimicrobial effect at the primary infection site for acute maxillary sinusitis has not previously been explored. This single-center, open-label study quantified the time course of sinus sterilization, described gatifloxacin exposure at the infection site, and posed the hypothesis that the use of continuous and quantitative time-related end points may allow for better characterization of drug effect with fewer patients than traditional clinical trial approaches. Of the 12 enrolled patients, 10 were clinically evaluable, from whom 7 pathogens were isolated: 4 Streptococcus pneumoniae, 2 staphylococci, and 1 Enterobacter aerogenes. The median predicted 24-h area under the curve (AUC) in sinus aspirates and plasma samples was 54.7 mg x h/L and 30.1 mg x h/L, respectively. The median 24-h AUC ratio for sinus aspirates and plasma samples was 1.51 (range, 0.88-2.23). For patients infected with pneumococci, the median time to sinus sterilization was 50 h. The use of quantitative time-related end points may be useful in evaluating the efficacy of antimicrobial agents with fewer patients.

Population Pharmacokinetics and Penetration into Prostatic, Seminal, and Vaginal Fluid for Ciprofloxacin, Levofloxacin, and Their Combination

“…Fluoroquinolones usually achieve tissue and body fluid concentrations that are higher than those of most β-lactams due to their physicochemical properties [68,69,70,71,72,73,74]. Our group applied body fluid penetration models for other quinolones and β-lactams [75,76,77,78,79,80,81].…”

Dosing Regimen Matters: the Importance of Early Intervention and Rapid Attainment of the Pharmacokinetic/Pharmacodynamic Target

“…For example, Ambrose et al (3) showed that in patients with acute maxillary sinusitis attributable to Streptococcus pneumoniae, high-dose gatifloxacin resulted in sinus sterilization within 24 to 72 h after the initiation of therapy. The median sinus gatifloxacin AUC/MIC ratio in these patients was 122.8.…”

Pharmacokinetics of azithromycin in serum and sinus fluid after administration of extended-release and immediate-release formulations in patients with acute bacterial sinusitis

“…doi:10.1016/j.ijantimicag.2008.01.027 Table 1 Collection times of blood and sinus aspirate First cohort of six subjects Second cohort of three subjects Thirteen sinus aspirate and blood samples were collected: 0 (pre first dose), 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96 and 120 h post first dose Seven sinus aspirate and blood samples were collected: 0 (pre first dose), 2, 4, 12, 24, 48 and 72 h post first dose drug assay over time using an indwelling sinus catheter [8]. To date, we are aware of only two other studies that have used this technique [8,9], therefore this study provides a unique insight into the pharmacokinetics of azithromycin in sinus fluid. In this trial, the pharmacokinetics of a single 2.0 g oral dose of AZ-ER versus AZ-IR 500 mg given orally once daily for 3 days was characterised in subjects with ABS using an indwelling sinus catheter (SinoJect ® ; Atos Medical AB, Hörby, Sweden).…”