Efficacy of a novel perfluorocarbon-based intrapulmonary drug delivery system

Abstract

Introduction: We sought to determine the efficacy of a novel intrapulmonary perfluorocarbon (PFC) based antibiotic delivery system in a rat model of pneumococcal pneumonia. Methods: Wistar rats (400-500 g) were inoculated with 8x10' type 3 pneumococcus via direct intratracheal (IT) injection. Twenty-four h after inoculation, rats received no treatment (control, n=15), 10 mg IM ampicillin (AMP, n =10), 10 ml lavage with an AMP containing (1 mg/ml) microparticulate dispersion in PFC (AMPPFC; Alliance Pharmaceutical Corp.; n=ll). Animals were monitored daily for survival for 10 days. AMP concentrations, were determined in serum and lung homogenates using a bioassay. The log-rank test with Bonferroni's correction was used to determine differences in mortality among groups. The null hypothesis was rejected for a critical p<0.017. Results: Mortality was significantly higher in controls than AMPPFC (100% vs 18%, p < 0.017). There was a trend favoring treatment with AMPPFC compared to AMP (18% vs 70% mortality, p<0.019). The table shows serum and lung antibiotic concentrations (n=2) Time (h) AMP (jig/ml) AMPPFC Qig/ml) Serum Lung Serum Lung 1 15 2 15 500 2 1 1 2 120 3 0 0 1 60 4 0 0 2 50 8 0 0 0 15 24 0 0 0 10 48 0 0 0 3 72 0 0 0 2 Conclusions: PFC-based IT antibiotic microparticulate formüations may be more effect than systemic antibiotic therapy alone in the treatment of severe pneumonia