Penetration of prulifloxacin into sinus mucosa of patients undergoing paranasal sinus elective endoscopic surgery.

The aim of this study was to assess the concentration of ulifloxacin, the active metabolite of prulifloxacin, in sinuses mucosa and plasma of patients with chronic rhinosinusitis, requiring sinus elective endoscopic surgery. Thirty-nine patients (30 males, 9 females; age range 22-77 years) with chronic sinusitis were enrolled, 35 were treated with the investigational medication. Samples from four untreated patients were used to validate the analytical method, while four treated patients dropped out before surgery. One 600 mg prulifloxacin tablet once daily was administered for 5 days before surgery. The last dosing was scheduled from 2 to 12 hours from tissue and plasma sampling. In each patient, two samples of paranasal sinus mucosa (from ethmoid and turbinate, respectively) and one blood sample were collected. Concentrations of ulifloxacin in plasma and sinuses mucosa were measured using validated bioanalytical LC/MS/MS methods. Individual and mean ulifloxacin concentrations in tissues were always higher than the relevant plasma levels. The highest concentrations were observed between 2.5 and 4.5 hours after the last dosing in all districts. The mean tissue/plasma ratios were 2.5 and 3.0 for ethmoid and turbinate, respectively. Data expressed as Area Under the Curves (AUC±SD) showed that ulifloxacin concentrations in the ethmoid were slightly higher (18.68±6.48 μg/g*h) than in turbinate (15.00±2.89 μg/g*h), and definitely higher than in plasma (6.32±1.14 μg/ml*h). The AUC ratios between tissues and plasma were 3.0 for ethmoides and 2.4 for turbinates. One patient reported two treatment-related episodes of diarrhea, which spontaneously resolved after the drug suspension. Results from this study seem to suggest that prulifloxacin showed good distribution in sinus tissues, where it reaches concentrations significantly higher than in plasma. These findings strongly call for confirmatory clinical trials in patients with bacterial rhinosinusitis.

RCT Entities:   Population Interventions Outcomes