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Background Pneumonia is a major cause of mortality in critically ill patients. Sitafloxacin, broad-spectrum fluoroquuinolone, has an in vitro activity against many drug-resistant pathogens causing pneumonia. The objectives of this study were to determine epithelial lining fluid (ELF) concentrations of sitafloxacin and compare those with plasma, including pharmacokinetic (PK) parameters in Thai critically ill patients. Methods Sitafloxacin concentrations were determined using LC–MS/MS assay. Twelve critically ill patients with pneumonia were enrolled to receive oral sitafloxacin 200 mg single dose. Serial blood samples were collected in each patient (seven time points) prior to dose and over 12-hour interval. BAL samples were collected once in each patient simultaneously with plasma sampling. Intrapulmonary penetration was evaluated as the ELF to unbound plasma concentration ratio calculated by fraction unbound related to albumin concentration in each patient. A compartment model was applied to describe plasma PK parameters using WinNonLin software. Results The median age was 57 years with median weight was 52 kg. The highest penetration ratio of ELF to unbound plasma concentrations based on median value was 1.3, observed during 5–6 hours (Table 1). The data fitted to one-compartment model that described absorption, distribution and elimination. PK parameters are presented in Table 2. Conclusion Oral sitafloxacin well penetrate into ELF at a penetration ratio of 130% related to unbound plasma in Thai critically ill patients. Sitafloxacin is a promising agent for treatment of lower respiratory tract infections caused by susceptible pathogens in intensive care unit.Table 1: Penetration Ratio Based on Median of Sitafloxacin Concentrations in Each Sampling Time BAL Fluid Sampling Time (hour) Sample (n) ELF Conc. (µg/mL) Unbound Plasma Conc. (µg/mL) Ratio ELF: Unbound Plasma Penetration (%) 0.5 - 2 3 0.09 0.29 0.3 30 3 - 4 3 0.50 0.91 0.5 50 5–6 3 0.84 0.64 1.3 130 7–9 3 0.22 0.42 0.5 50Table 2: PK parameters of sitafloxacin 200 mg single dose based on the median values (min–max). PK Parameters Plasma ELF T max (h) 3.7 (1–8) 5.5 C max (µg/mL) 1.5 (0.48–1.82) 0.84 K a (h−1) 10.84 (3.64–48.49) NA CL/F (mL/minute) 221.62 (45.13–533.22) NA V/F (L) 148.92 (100.88–361.81) NA AUC0–12 (µg·hour/mL) 10.84 (3.64–48.49) NA K a, absorption rate constant; NA, not applicable. Disclosures T. Paiboonvong, Daiichi Sankyo (Thailand) LTD.: Grant support, Research support. V. Tangsujaritvijit, Ramathibodi Hospital: Grant support, Research support.

1423. Plasma and Intrapulmonary Pharmacokinetics of Sitafloxacin in Thai Critically Ill Patients With Pneumonia